Pub Date : 2024-04-08DOI: 10.1007/s13167-024-00357-5
Ousman Bajinka, Serge Yannick Ouedraogo, Olga Golubnitschaja, Na Li, Xianquan Zhan
Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease).
The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches.
Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles—all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subp
{"title":"Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine","authors":"Ousman Bajinka, Serge Yannick Ouedraogo, Olga Golubnitschaja, Na Li, Xianquan Zhan","doi":"10.1007/s13167-024-00357-5","DOIUrl":"https://doi.org/10.1007/s13167-024-00357-5","url":null,"abstract":"<p>Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease).</p><p>The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches.</p><p>Finally, exemplified in this article metabolic phenotyping is instrumental for innovative population screening, health risk assessment, predictive multi-level diagnostics, targeted prevention, and treatment algorithms tailored to personalized patient profiles—all are essential pillars in the paradigm change from reactive medical services to 3PM approach in overall management of lung cancers. This article highlights the 3PM relevant innovation focused on energy metabolism as the hub to advance NSCLC management benefiting vulnerable subp","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-04DOI: 10.1007/s13167-024-00352-w
Jingru Yang, Serge Yannick Ouedraogo, Jingjing Wang, Zhijun Li, Xiaoxia Feng, Zhen Ye, Shu Zheng, Na Li, Xianquan Zhan
Relevance
The proteasome is a crucial mechanism that regulates protein fate and eliminates misfolded proteins, playing a significant role in cellular processes. In the context of lung cancer, the proteasome’s regulatory function is closely associated with the disease’s pathophysiology, revealing multiple connections within the cell. Therefore, studying proteasome inhibitors as a means to identify potential pathways in carcinogenesis and metastatic progression is crucial in in-depth insight into its molecular mechanism and discovery of new therapeutic target to improve its therapy, and establishing effective biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized treatment for lung squamous carcinoma in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine).
Methods
This study identified differentially expressed proteasome genes (DEPGs) in lung squamous carcinoma (LUSC) and developed a gene signature validated through Kaplan–Meier analysis and ROC curves. The study used WGCNA analysis to identify proteasome co-expression gene modules and their interactions with the immune system. NMF analysis delineated distinct LUSC subtypes based on proteasome gene expression patterns, while ssGSEA analysis quantified immune gene-set abundance and classified immune subtypes within LUSC samples. Furthermore, the study examined correlations between clinicopathological attributes, immune checkpoints, immune scores, immune cell composition, and mutation status across different risk score groups, NMF clusters, and immunity clusters.
Results
This study utilized DEPGs to develop an eleven-proteasome gene-signature prognostic model for LUSC, which divided samples into high-risk and low-risk groups with significant overall survival differences. NMF analysis identified six distinct LUSC clusters associated with overall survival. Additionally, ssGSEA analysis classified LUSC samples into four immune subtypes based on the abundance of immune cell infiltration with clinical relevance. A total of 145 DEGs were identified between high-risk and low-risk score groups, which had significant biological effects. Moreover, PSMD11 was found to promote LUSC progression by depending on the ubiquitin–proteasome system for degradation.
Conclusions
Ubiquitinated proteasome genes were effective in developing a prognostic model for LUSC patients. The study emphasized the critical role of proteasomes in LUSC processes, such as drug sensitivity, immune microenvironment, and mutation status. These data will contribute to the clinically relevant stratification of LUSC patients for personalized 3P medical approach. Further, we also recommend the application of the ubiquitinated proteasome system in multi-level diagnostics including multi-
{"title":"Clinically relevant stratification of lung squamous carcinoma patients based on ubiquitinated proteasome genes for 3P medical approach","authors":"Jingru Yang, Serge Yannick Ouedraogo, Jingjing Wang, Zhijun Li, Xiaoxia Feng, Zhen Ye, Shu Zheng, Na Li, Xianquan Zhan","doi":"10.1007/s13167-024-00352-w","DOIUrl":"https://doi.org/10.1007/s13167-024-00352-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Relevance</h3><p>The proteasome is a crucial mechanism that regulates protein fate and eliminates misfolded proteins, playing a significant role in cellular processes. In the context of lung cancer, the proteasome’s regulatory function is closely associated with the disease’s pathophysiology, revealing multiple connections within the cell. Therefore, studying proteasome inhibitors as a means to identify potential pathways in carcinogenesis and metastatic progression is crucial in in-depth insight into its molecular mechanism and discovery of new therapeutic target to improve its therapy, and establishing effective biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized treatment for lung squamous carcinoma in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study identified differentially expressed proteasome genes (DEPGs) in lung squamous carcinoma (LUSC) and developed a gene signature validated through Kaplan–Meier analysis and ROC curves. The study used WGCNA analysis to identify proteasome co-expression gene modules and their interactions with the immune system. NMF analysis delineated distinct LUSC subtypes based on proteasome gene expression patterns, while ssGSEA analysis quantified immune gene-set abundance and classified immune subtypes within LUSC samples. Furthermore, the study examined correlations between clinicopathological attributes, immune checkpoints, immune scores, immune cell composition, and mutation status across different risk score groups, NMF clusters, and immunity clusters.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>This study utilized DEPGs to develop an eleven-proteasome gene-signature prognostic model for LUSC, which divided samples into high-risk and low-risk groups with significant overall survival differences. NMF analysis identified six distinct LUSC clusters associated with overall survival. Additionally, ssGSEA analysis classified LUSC samples into four immune subtypes based on the abundance of immune cell infiltration with clinical relevance. A total of 145 DEGs were identified between high-risk and low-risk score groups, which had significant biological effects. Moreover, PSMD11 was found to promote LUSC progression by depending on the ubiquitin–proteasome system for degradation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Ubiquitinated proteasome genes were effective in developing a prognostic model for LUSC patients. The study emphasized the critical role of proteasomes in LUSC processes, such as drug sensitivity, immune microenvironment, and mutation status. These data will contribute to the clinically relevant stratification of LUSC patients for personalized 3P medical approach. Further, we also recommend the application of the ubiquitinated proteasome system in multi-level diagnostics including multi-","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-27DOI: 10.1007/s13167-024-00356-6
Abstract
Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990–2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep–wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurat
Abstract Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined.据估计,中风造成的全球经济负担每年超过 8910 亿美元。在三十年内(1990-2019 年),发病率增加了 70%,死亡率增加了 43%,患病率增加了 102%,残疾调整寿命年数增加了 143%。在全球记录在案的 1 亿多中风患者中,约 76% 为缺血性中风(IS)患者。从背景上看,缺血性中风已成为研究人员、医疗保健行业、经济学家和政策制定者等多专业群体关注的焦点。缺血性中风的风险因素为初级(亚健康状态)和二级(临床表现为导致中风风险的并发症)护理中采取具有成本效益的预防干预措施提供了足够的空间。这些风险是相互关联的。例如,久坐不动的生活方式和有毒环境都会导致线粒体压力、全身低度炎症和加速老化;炎症是一种与加速老化和不良中风预后相关的低度炎症。压力超载、线粒体生物能降低和低镁血症与包括青少年在内的所有年龄组的全身血管痉挛和心脑缺血性病变有关。叶酸含量低但富含红肉、加工肉类、精制谷物和含糖饮料的不平衡膳食模式与高同型半胱氨酸血症、全身炎症、小血管疾病和 IS 风险增加有关。由欧洲预测、预防和个性化医学协会(EPMA)推动的针对人群中弱势群体的 3PM 研究正在进行中,研究结果表明,EPMA 专家小组在此报告的基于泪液的健康风险评估、作为重要生物传感器的线粒体以及基于人工智能的多专业数据解读等对患者友好的非侵入性综合方法前景广阔。收集的数据表明,与 IS 相关的风险和相应的分子途径是相互关联的。例如,IS 所涉及的分子模式与作为糖尿病患者 IS 风险早期指标的糖尿病视网膜病变之间存在明显的重叠。例如,5-氨基乙酰丙酸/途径也是有丝分裂模式改变、失眠、压力调节和微生物群-肠-脑串联调节的特征。此外,神经酰胺被认为是心脏代谢疾病中氧化应激和炎症的介质,会对线粒体呼吸链功能和裂变/融合活动、睡眠-觉醒行为改变、血管僵硬和重塑产生负面影响。黄嘌呤/途径调节参与线粒体平衡、压力驱动的焦虑行为以及动脉僵化的分子机制。为了评估个人健康风险,应用机器学习(人工智能工具)对多参数分析进行准确的数据解读至关重要。论文中介绍的内容包括年轻人群和老年人的需求、初级和二级医疗中的个性化风险评估、成本效益、创新技术和筛查计划的应用、针对专业人员和普通民众的先进教育措施--所有这些都是 EPMA 倡导的整体信息系统管理中从被动医疗服务向 3PM 模式转变的重要支柱。
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Pub Date : 2024-02-22DOI: 10.1007/s13167-024-00353-9
Fernando J. Regateiro, Henriqueta Silva, Manuel C. Lemos, Gabriela Moura, Pedro Torres, André Dias Pereira, Luís Dias, Pedro L. Ferreira, Sara Amaral, Manuel A. S. Santos
Multidisciplinary team from three universities based in the “Centro” Region of Portugal developed diverse approaches as parts of a project dedicated to enhancing and expanding Predictive, Preventive, and Personalized Medicine (3PM) in the Region. In a sense, outcomes acted as a proof-of-concept, in that they demonstrated the feasibility, but also the relevance of the approaches. The accomplishments comprise defining a new regional strategy for implementing 3PM within the Region, training of human resources in genomic sequencing, and generating good practices handbooks dedicated to diagnostic testing via next-generation sequencing, to legal and ethical concerns, and to knowledge transfer and entrepreneurship, aimed at increasing literacy on 3PM approaches. Further approaches also included support for entrepreneurship development and start-ups, and diverse and relevant initiatives aimed at increasing literacy relevant to 3PM. Efforts to enhance literacy encompassed citizens across the board, from patients and high school students to health professionals and health students. This focus on empowerment through literacy involved a variety of initiatives, including the creation of an illustrated book on genomics and the production of two theater plays centered on genetics. Additionally, authors stressed that genomic tools are relevant, but they are not the only resources 3PM is based on. Thus, they defend that other initiatives intended to enable citizens to take 3PM should include multi-omics and, having in mind the socio-economic burden of chronic diseases, suboptimal health status approaches in the 3PM framework should also be considered, in order to anticipate medical intervention in the subclinical phase.
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Pub Date : 2024-02-19DOI: 10.1007/s13167-024-00354-8
Jie Fang, Jielong Wu, Ganji Hong, Liangcheng Zheng, Lu Yu, Xiuping Liu, Pan Lin, Zhenzhen Yu, Dan Chen, Qing Lin, Chuya Jing, Qiuhong Zhang, Chen Wang, Jiedong Zhao, Xiaodong Yuan, Chunfang Wu, Zhaojie Zhang, Mingwei Guo, Junde Zhang, Jingjing Zheng, Aidi Lei, Tengkun Zhang, Quan Lan, Lingsheng Kong, Xinrui Wang, Zhanxiang Wang, Qilin Ma
Background/aims
The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a “vicious cycle.” Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer.
Methods
Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research.
Results
The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram’s strong performance.
Conclusions
The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM.
背景/摘要 癌症与中风的相互促进是由于共同的危险因素(如代谢途径和分子靶点)发生了变化,从而形成了 "恶性循环"。癌症在缺血性脑卒中(IS)的发病机制中起着直接或间接的作用,再加上缺血性脑卒中患者在治疗和临床管理中采用的反应性医疗方法,导致这些患者面临与隐匿性癌症相关的临床挑战。缺乏可靠而简单的工具阻碍了预测、预防和个性化医疗(PPPM/3PM)方法的有效性。因此,我们开展了一项多中心研究,重点关注多参数分析,以促进隐匿性癌症的早期诊断和癌症相关中风的个性化治疗。训练数据集包括136名并发癌症的IS患者,与对照组按1:1的比例匹配。通过逻辑回归和五种可供选择的机器学习模型来评估 IS 患者罹患隐匿性癌症的风险。随后,选择预测效力最高的模型创建一个提名图,作为临床实践中预测诊断的定量工具。内部验证采用了十倍交叉验证,外部验证涉及来自六个中心的 239 名 IS 患者。验证包括接收器操作特征曲线(ROC)、校准曲线、决策曲线分析(DCA)以及与先前研究模型的比较。结果最终预测模型以逻辑回归为基础,包含以下变量:缺血性病变区域、多血管区域、高血压、D-二聚体、纤维蛋白原(FIB)和血红蛋白(Hb)。在训练数据集中,提名图的 ROC 曲线下面积(AUC)为 0.871,在外部测试数据集中为 0.834。结论 该提名图能对住院的 IS 患者进行早期隐匿性癌症诊断,有助于准确确定 IS 的病因,同时促进 IS 的分层,使个性化治疗成为可能。基于IS患者常规临床检查指标的在线提名图为PPPM框架下的二级护理提供了一个具有成本效益的平台。
{"title":"Cancer screening in hospitalized ischemic stroke patients: a multicenter study focused on multiparametric analysis to improve management of occult cancers","authors":"Jie Fang, Jielong Wu, Ganji Hong, Liangcheng Zheng, Lu Yu, Xiuping Liu, Pan Lin, Zhenzhen Yu, Dan Chen, Qing Lin, Chuya Jing, Qiuhong Zhang, Chen Wang, Jiedong Zhao, Xiaodong Yuan, Chunfang Wu, Zhaojie Zhang, Mingwei Guo, Junde Zhang, Jingjing Zheng, Aidi Lei, Tengkun Zhang, Quan Lan, Lingsheng Kong, Xinrui Wang, Zhanxiang Wang, Qilin Ma","doi":"10.1007/s13167-024-00354-8","DOIUrl":"https://doi.org/10.1007/s13167-024-00354-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background/aims</h3><p>The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a “vicious cycle.” Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram’s strong performance.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139902286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-15DOI: 10.1007/s13167-024-00350-y
Yaling Liu, Hai Xie, Xinyu Zhao, Jiannan Tang, Zhen Yu, Zhenquan Wu, Ruyin Tian, Yi Chen, Miaohong Chen, Dimitrios P. Ntentakis, Yueshanyi Du, Tingyi Chen, Yarou Hu, Sifan Zhang, Baiying Lei, Guoming Zhang
Purpose
We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and health conditions to satisfy urgent needs of ophthalmologists.
Methods
We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results.
Results
Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62% (95% CI, 94.34%-94.90%), 94.07% (95% CI, 93.32%-94.82%), 90.56% (95% CI, 88.64%-92.48%), 92.34% (95% CI, 91.87%-92.81%), 91.15% (95% CI, 90.37%-91.93%), and 99.08% (95% CI, 99.07%-99.09%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45% (95% CI, 96.37%-96.53%), 95.86% (95% CI, 94.56%-97.16%), 94.37% (95% CI, 93.95%-94.79%), 95.03% (95% CI, 94.45%-95.61%), 94.43% (95% CI, 93.96%-94.90%), and 99.51% (95% CI, 99.51%-99.51%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities.
Conclusions
IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM / 3PM) in the treatment of infantile fundus diseases.
{"title":"Automated detection of nine infantile fundus diseases and conditions in retinal images using a deep learning system","authors":"Yaling Liu, Hai Xie, Xinyu Zhao, Jiannan Tang, Zhen Yu, Zhenquan Wu, Ruyin Tian, Yi Chen, Miaohong Chen, Dimitrios P. Ntentakis, Yueshanyi Du, Tingyi Chen, Yarou Hu, Sifan Zhang, Baiying Lei, Guoming Zhang","doi":"10.1007/s13167-024-00350-y","DOIUrl":"https://doi.org/10.1007/s13167-024-00350-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and health conditions to satisfy urgent needs of ophthalmologists.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62% (95% CI, 94.34%-94.90%), 94.07% (95% CI, 93.32%-94.82%), 90.56% (95% CI, 88.64%-92.48%), 92.34% (95% CI, 91.87%-92.81%), 91.15% (95% CI, 90.37%-91.93%), and 99.08% (95% CI, 99.07%-99.09%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45% (95% CI, 96.37%-96.53%), 95.86% (95% CI, 94.56%-97.16%), 94.37% (95% CI, 93.95%-94.79%), 95.03% (95% CI, 94.45%-95.61%), 94.43% (95% CI, 93.96%-94.90%), and 99.51% (95% CI, 99.51%-99.51%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM / 3PM) in the treatment of infantile fundus diseases.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-15DOI: 10.1007/s13167-024-00355-7
Xuening Jian, Wenxin Sun, Jie Zhang, Qiaoyun Zhang, Xiaoni Meng, Huimin Lu, Deqiang Zheng, Lijuan Wu, Youxin Wang
Introduction
Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM).
Methods
We included 440,551 participants from the UK Biobank between the baseline visit (2006–2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality.
Results
During a median follow-up of 13.74 years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93–0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90–0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34–1.36), CVD-specific (HR: 1.47, 95% CI: 1.44–1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20–1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality.
Conclusions
Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM.
{"title":"Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants","authors":"Xuening Jian, Wenxin Sun, Jie Zhang, Qiaoyun Zhang, Xiaoni Meng, Huimin Lu, Deqiang Zheng, Lijuan Wu, Youxin Wang","doi":"10.1007/s13167-024-00355-7","DOIUrl":"https://doi.org/10.1007/s13167-024-00355-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We included 440,551 participants from the UK Biobank between the baseline visit (2006–2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>During a median follow-up of 13.74 years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93–0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90–0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34–1.36), CVD-specific (HR: 1.47, 95% CI: 1.44–1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20–1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09DOI: 10.1007/s13167-024-00351-x
Abstract
Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles—all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.
{"title":"Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations","authors":"","doi":"10.1007/s13167-024-00351-x","DOIUrl":"https://doi.org/10.1007/s13167-024-00351-x","url":null,"abstract":"<h3>Abstract</h3> <p>Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles—all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139764651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The effects of psychological factors on suboptimal health status (SHS) have been widely described; however, mechanisms behind the complex relationships among the Big Five personality traits and SHS are unclear. Identifying people with specific traits who are susceptible to SHS will help improve life quality and reduce the chronic disease burden under the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). This study investigated the relationships among personality traits and SHS. It also explored whether perceived stress plays a mediating role in SHS development.
Method
A nationwide cross-sectional survey based on multistage random sampling was conducted in 148 cities in China between June 20 and August 31, 2022. Personality traits, perceived stress, and SHS were evaluated using the Big Five Inventory-10 (BFI-10), the 4-item Perceived Stress Scale (PSS-4), and the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF), respectively. Pearson’s correlation analysis was employed to examine the associations between personality traits, perceived stress, and SHS. Structural equation modeling (SEM) was used to discern the mediating role of perceived stress in the relationships among personality traits and SHS.
Result
A total of 22,897 participants were enrolled in this study, among whom the prevalence of SHS was 52.9%. SHS was negatively correlated with three trait dimensions (i.e., extraversion, agreeableness, and conscientiousness) but positively correlated with neuroticism. Meanwhile, stress was negatively correlated with extraversion, agreeableness, conscientiousness, and openness, whereas it was positively correlated with neuroticism. The SEM results showed that, when adjusting for covariates (i.e., gender, age, BMI, educational level, current residence, marital status, and occupational status), higher agreeableness (β = − 0.049, P < 0.001) and conscientiousness (β = − 0.103, P < 0.001) led to lower SHS prevalence, higher neuroticism (β = 0.130, P < 0.001), and openness (β = 0.026, P < 0.001) caused SHS to be more prevalent. Perceived stress played a partial mediating role in the relationships among personality traits and SHS, respectively, contributing 41.3%, 35.9%, and 32.5% to the total effects of agreeableness, conscientiousness, and neuroticism on SHS. Additionally, the mediating impact of stress was significant even though extraversion had no direct effect on SHS.
Conclusion
This study revealed a high prevalence of SHS in Chinese residents. Personality traits significantly influenced SHS rates, which perceived stress tended to mediate. From a PPPM perspective, early screening and targeted intervention for people with neuroticism (as well as stress allevi
{"title":"The mediating effect of perceived stress on the relationship between big five personality traits and suboptimal health status in Chinese population: a nationwide survey in the framework of predictive, preventive, and personalized medicine","authors":"Qihua Guan, Hualei Dong, Zhihui Zhang, Zheng Guo, Zi Lin, Hui Niu, Yibo Wu, Haifeng Hou","doi":"10.1007/s13167-023-00349-x","DOIUrl":"https://doi.org/10.1007/s13167-023-00349-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The effects of psychological factors on suboptimal health status (SHS) have been widely described; however, mechanisms behind the complex relationships among the Big Five personality traits and SHS are unclear. Identifying people with specific traits who are susceptible to SHS will help improve life quality and reduce the chronic disease burden under the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). This study investigated the relationships among personality traits and SHS. It also explored whether perceived stress plays a mediating role in SHS development.</p><h3 data-test=\"abstract-sub-heading\">Method</h3><p>A nationwide cross-sectional survey based on multistage random sampling was conducted in 148 cities in China between June 20 and August 31, 2022. Personality traits, perceived stress, and SHS were evaluated using the Big Five Inventory-10 (BFI-10), the 4-item Perceived Stress Scale (PSS-4), and the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF), respectively. Pearson’s correlation analysis was employed to examine the associations between personality traits, perceived stress, and SHS. Structural equation modeling (SEM) was used to discern the mediating role of perceived stress in the relationships among personality traits and SHS.</p><h3 data-test=\"abstract-sub-heading\">Result</h3><p>A total of 22,897 participants were enrolled in this study, among whom the prevalence of SHS was 52.9%. SHS was negatively correlated with three trait dimensions (i.e., extraversion, agreeableness, and conscientiousness) but positively correlated with neuroticism. Meanwhile, stress was negatively correlated with extraversion, agreeableness, conscientiousness, and openness, whereas it was positively correlated with neuroticism. The SEM results showed that, when adjusting for covariates (i.e., gender, age, BMI, educational level, current residence, marital status, and occupational status), higher agreeableness (<i>β</i> = − 0.049, <i>P</i> < 0.001) and conscientiousness (<i>β</i> = − 0.103, <i>P</i> < 0.001) led to lower SHS prevalence, higher neuroticism (<i>β</i> = 0.130, <i>P</i> < 0.001), and openness (<i>β</i> = 0.026, <i>P</i> < 0.001) caused SHS to be more prevalent. Perceived stress played a partial mediating role in the relationships among personality traits and SHS, respectively, contributing 41.3%, 35.9%, and 32.5% to the total effects of agreeableness, conscientiousness, and neuroticism on SHS. Additionally, the mediating impact of stress was significant even though extraversion had no direct effect on SHS.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study revealed a high prevalence of SHS in Chinese residents. Personality traits significantly influenced SHS rates, which perceived stress tended to mediate. From a PPPM perspective, early screening and targeted intervention for people with neuroticism (as well as stress allevi","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138572346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-06DOI: 10.1007/s13167-023-00348-y
Wenshuang Jia, Xiaoxia Gong, Zhen Ye, Na Li, Xianquan Zhan
Protein tyrosine nitration is a selectively and reversible important post-translational modification, which is closely related to oxidative stress. Astrocytoma is the most common neuroepithelial tumor with heterogeneity and complexity. In the past, the diagnosis of astrocytoma was based on the histological and clinical features, and the treatment methods were nothing more than surgery-assisted radiotherapy and chemotherapy. Obviously, traditional methods short falls an effective treatment for astrocytoma. In late 2021, the World Health Organization (WHO) adopted molecular biomarkers in the comprehensive diagnosis of astrocytoma, such as IDH-mutant and DNA methylation, which enabled the risk stratification, classification, and clinical prognosis prediction of astrocytoma to be more correct. Protein tyrosine nitration is closely related to the pathogenesis of astrocytoma. We hypothesize that nitroproteome is significantly different in astrocytoma relative to controls, which leads to establishment of nitroprotein biomarkers for patient stratification, diagnostics, and prediction of disease stages and severity grade, targeted prevention in secondary care, treatment algorithms tailored to individualized patient profile in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Nitroproteomics based on gel electrophoresis and tandem mass spectrometry is an effective tool to identify the nitroproteins and effective biomarkers in human astrocytomas, clarifying the biological roles of oxidative/nitrative stress in the pathophysiology of astrocytomas, functional characteristics of nitroproteins in astrocytomas, nitration-mediated signal pathway network, and early diagnosis and treatment of astrocytomas. The results finds that these nitroproteins are enriched in mitotic cell components, which are related to transcription regulation, signal transduction, controlling subcellular organelle events, cell perception, maintaining cell homeostasis, and immune activity. Eleven statistically significant signal pathways are identified in astrocytoma, including remodeling of epithelial adherens junctions, germ cell-sertoli cell junction signaling, 14-3-3-mediated signaling, phagosome maturation, gap junction signaling, axonal guidance signaling, assembly of RNA polymerase III complex, and TREM1 signaling. Furthermore, protein tyrosine nitration is closely associated with the therapeutic effects of protein drugs, and molecular mechanism and drug targets of cancer. It provides valuable data for studying the protein nitration biomarkers, molecular mechanisms, and therapeutic targets of astrocytoma towards PPPM (3P medicine) practice.
蛋白质酪氨酸硝化是一种选择性和可逆性的重要翻译后修饰,与氧化应激密切相关。星形细胞瘤是最常见的神经上皮肿瘤,具有异质性和复杂性。过去,星形细胞瘤的诊断主要依据组织学和临床特征,治疗方法不外乎手术辅助放疗和化疗。显然,传统方法并不能有效治疗星形细胞瘤。2021年底,世界卫生组织(WHO)在星形细胞瘤的综合诊断中采用了IDH突变、DNA甲基化等分子生物标志物,使星形细胞瘤的危险分层、分类和临床预后预测更加准确。蛋白酪氨酸硝化与星形细胞瘤的发病机制密切相关。我们假设星形细胞瘤的硝基蛋白组与对照组有显著差异,从而建立硝基蛋白生物标志物,用于患者分层、诊断、疾病分期和严重程度等级预测、二级护理中的针对性预防,以及在预测、预防和个性化医学(PPPM;3P 医学)框架内根据患者个体情况定制治疗算法。基于凝胶电泳和串联质谱的硝基蛋白组学是鉴定人类星形细胞瘤中硝基蛋白和有效生物标志物的有效工具,可阐明氧化/硝化应激在星形细胞瘤病理生理学中的生物学作用、星形细胞瘤中硝基蛋白的功能特征、硝化介导的信号通路网络以及星形细胞瘤的早期诊断和治疗。研究结果发现,这些硝基蛋白富含有丝分裂细胞成分,与转录调控、信号转导、控制亚细胞器事件、细胞感知、维持细胞稳态和免疫活动有关。在星形细胞瘤中发现了 11 条具有统计学意义的信号通路,包括上皮粘连连接重塑、生殖细胞-凋亡细胞连接信号转导、14-3-3 介导的信号转导、吞噬体成熟、间隙连接信号转导、轴突导向信号转导、RNA 聚合酶 III 复合物组装和 TREM1 信号转导。此外,蛋白质酪氨酸硝化与蛋白质药物的治疗效果、癌症的分子机制和药物靶点密切相关。该研究为研究星形细胞瘤的蛋白硝化生物标志物、分子机制和治疗靶点提供了宝贵的数据,有助于PPPM(3P医学)的实践。
{"title":"Nitroproteomics is instrumental for stratification and targeted treatments of astrocytoma patients: expert recommendations for advanced 3PM approach with improved individual outcomes","authors":"Wenshuang Jia, Xiaoxia Gong, Zhen Ye, Na Li, Xianquan Zhan","doi":"10.1007/s13167-023-00348-y","DOIUrl":"https://doi.org/10.1007/s13167-023-00348-y","url":null,"abstract":"<p>Protein tyrosine nitration is a selectively and reversible important post-translational modification, which is closely related to oxidative stress. Astrocytoma is the most common neuroepithelial tumor with heterogeneity and complexity. In the past, the diagnosis of astrocytoma was based on the histological and clinical features, and the treatment methods were nothing more than surgery-assisted radiotherapy and chemotherapy. Obviously, traditional methods short falls an effective treatment for astrocytoma. In late 2021, the World Health Organization (WHO) adopted molecular biomarkers in the comprehensive diagnosis of astrocytoma, such as IDH-mutant and DNA methylation, which enabled the risk stratification, classification, and clinical prognosis prediction of astrocytoma to be more correct. Protein tyrosine nitration is closely related to the pathogenesis of astrocytoma. We hypothesize that nitroproteome is significantly different in astrocytoma relative to controls, which leads to establishment of nitroprotein biomarkers for patient stratification, diagnostics, and prediction of disease stages and severity grade, targeted prevention in secondary care, treatment algorithms tailored to individualized patient profile in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Nitroproteomics based on gel electrophoresis and tandem mass spectrometry is an effective tool to identify the nitroproteins and effective biomarkers in human astrocytomas, clarifying the biological roles of oxidative/nitrative stress in the pathophysiology of astrocytomas, functional characteristics of nitroproteins in astrocytomas, nitration-mediated signal pathway network, and early diagnosis and treatment of astrocytomas. The results finds that these nitroproteins are enriched in mitotic cell components, which are related to transcription regulation, signal transduction, controlling subcellular organelle events, cell perception, maintaining cell homeostasis, and immune activity. Eleven statistically significant signal pathways are identified in astrocytoma, including remodeling of epithelial adherens junctions, germ cell-sertoli cell junction signaling, 14-3-3-mediated signaling, phagosome maturation, gap junction signaling, axonal guidance signaling, assembly of RNA polymerase III complex, and TREM1 signaling. Furthermore, protein tyrosine nitration is closely associated with the therapeutic effects of protein drugs, and molecular mechanism and drug targets of cancer. It provides valuable data for studying the protein nitration biomarkers, molecular mechanisms, and therapeutic targets of astrocytoma towards PPPM (3P medicine) practice.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}