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Procalcitonin Guided Antibiotic Stewardship. 前降钙素指导下的抗生素管理。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-17 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241298197
Girum Tesfaye Kiya, Elsah Tegene Asefa, Gemeda Abebe, Zeleke Mekonnen

Despite infection and sepsis being a major public health challenge, early detection and timely management are often hindered by several factors. These includes the similarity of clinical presentations between infectious and non-infectious conditisons, as well as limitations of current diagnostic methods such as lengthy turnaround times and low sensitivity. Consequently, there is increasing interest in identifying biomarkers that can quickly and accurately differentiate bacterial sepsis from other inflammatory processes, whether infectious or non-infectious. Procalcitonin has emerged as one of the most extensively studied and utilized biomarkers in managing infection and sepsis, especially within the framework of antibiotic stewardship. This review aims to examine the role of Procalcitonin in guiding antibiotic stewardship. It explores the production and release of procalcitonin and its relevance in the context of infection and sepsis. The discussion focus on the clinical and economic impacts of using procalcitonin to guide the initiation and discontinuation of antibiotics in managing these conditions.

尽管感染和败血症是一项重大的公共卫生挑战,但早期发现和及时处理往往受到几个因素的阻碍。这些因素包括感染性和非感染性脓毒症的临床表现相似,以及当前诊断方法的局限性,如周转时间长和灵敏度低。因此,人们对确定生物标志物的兴趣与日俱增,这些生物标志物可以快速、准确地将细菌性败血症与其他炎症过程(无论是感染性还是非感染性)区分开来。降钙素原已成为在管理感染和败血症方面研究和使用最广泛的生物标志物之一,尤其是在抗生素管理框架内。本综述旨在探讨降钙素原在指导抗生素管理中的作用。它探讨了降钙素原的产生和释放及其与感染和败血症的相关性。讨论的重点是使用降钙素原指导抗生素的使用和停用对临床和经济的影响。
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引用次数: 0
Bladder Cancer Treatments in the Age of Personalized Medicine: A Comprehensive Review of Potential Radiosensitivity Biomarkers. 个性化医疗时代的膀胱癌治疗:潜在放射敏感性生物标志物的全面回顾。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241297168
Charbel Feghaly, Rafka Challita, Hanine Bou Hadir, Tala Mobayed, Tarek Al Bitar, Mohammad Harbi, Hala Ghorayeb, Rana El-Hassan, Larry Bodgi

Bladder cancer is one of the most frequently diagnosed cancers in men. While cystectomy remains the primary treatment, advances in radiotherapy and chemotherapy have highlighted the value of bladder-preserving strategies, which can also enhance patients' quality of life. Despise these advances, around 20% of patients may still require salvage cystectomy due to tumor radioresistance. This underscores the need to develop radiosensitivity predictive assays. Radiotherapy acts by inducing DNA damage, primarily through DNA double-strand breaks, which can significantly affect treatment outcomes if left unrepaired. In addition to activating DNA repair pathways, the response to radiation also involves the tumor microenvironment, cell death pathways, immune responses and different types of cell death and proliferation receptors. In recent years, personalized medicine, which tailors treatments to individual patients, has gained increasing attention in cancer care. The development of chemo- and radiosensitivity predictive assays has become a key focus of cancer research. Despite the potential impact of such assays on bladder cancer treatment, there is still no reliable test that can help clinicians and informs patients in choosing the best treatment. This review aims to highlight studies that attempted to characterize bladder cancer radiosensitivity and to discuss the potential biomarkers that could be used to develop bladder cancer radiosensitivity predictive assays.

膀胱癌是男性最常见的癌症之一。虽然膀胱切除术仍是主要的治疗方法,但放疗和化疗的进步凸显了保留膀胱策略的价值,这也能提高患者的生活质量。尽管取得了这些进步,但仍有约 20% 的患者可能因肿瘤放射抵抗而需要进行挽救性膀胱切除术。这凸显了开发放射敏感性预测测定的必要性。放疗通过诱导DNA损伤发挥作用,主要是通过DNA双链断裂,如果不及时修复,会严重影响治疗效果。除了激活DNA修复途径外,辐射反应还涉及肿瘤微环境、细胞死亡途径、免疫反应以及不同类型的细胞死亡和增殖受体。近年来,为患者量身定制治疗方案的个性化医疗在癌症治疗领域日益受到关注。化疗和放射敏感性预测测定的开发已成为癌症研究的重点。尽管这种检测方法对膀胱癌治疗有潜在影响,但目前仍没有可靠的检测方法能帮助临床医生和告知患者选择最佳治疗方法。本综述旨在重点介绍试图描述膀胱癌放射敏感性的研究,并讨论可用于开发膀胱癌放射敏感性预测测定的潜在生物标记物。
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引用次数: 0
Systematic Analysis and Insights Into the Mutation Spectrum and Ethnic Differences in ATP7B Mutations Associated With Wilson Disease. 系统分析与威尔逊氏病相关的 ATP7B 基因突变谱和种族差异。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241297169
Thuan Duc Lao, Thuy Ai Huyen Le

Background: ATP7B (ATPase copper transporting beta gene) is constituted of 21 exons, and codes for a 1465 amino acid. The protein of ATP7B plays an key role of copper metabolism. Many previous reports indicated that mutations in ATP7B are well known to cause defective copper transporting copper-transporting ATPase 2 protein leading to the accumulation of copper, resulting the Wilson disease.

Objectives: The meta-analysis was performed to comprehensive gain a thorough grasp of the spectrum of genetic variations.

Design: A meta-analysis was conducted according to the guiding of PRISMA. aiming to assess the diversity and frequency of mutations in the ATP7B gene, with an emphasis on mutations located within specific exons.

Data sources and methods: The dataset of detected mutations within their positions, types as well as nomenclature, were recorded from previous studies (spanning the year from 2013 to 2023). The analysis focused on exon-specific variations and their prevalence across different populations.

Results: A total of 40 studies were enrolled into current data analysis. Our comprehensive study revealed a variety of mutations, most notably over 50% of single nucleotide changes described, distributed over the 21 exons of the gene. Focusing on the exon 8, itisplayed the most diversity of mutations, with 18 studies identifying 53 unique variants, the majority of which were missense mutations (81.13%). Additionally, the variations c.2333G>A/T (p.R778Q/L), c.2305A>G (p.M769V), c.2336G>A (p.W779*), and c.2304dupC (p.M769HfsX26) are reported in many populations. The weighted mean of variants' proportion was used to calculate the pooled estimate of these percentages, which were 14.19% for c.2333G>A/T (p.R778Q/L), 2.70% for c.2305A>G (p.M769V), 1.42% for c.2336G>A (p.W779*), and 2.33% for c.2304dupC (p.M769HfsX26).

Conclusion: This design demonstrate to identify the spectrum of ATP7B gene's mutations, especially exon 8, offering important insights into the prevalence and significance of exon 8 mutations. Understanding the mutation in the ATP7B gene offers insights into the mechanisms behind WD and guides strategies for diagnosis and treatment.

背景:ATP7B(ATPase copper transporting beta gene)由 21 个外显子组成,编码 1465 个氨基酸。ATP7B 蛋白在铜代谢中起着关键作用。此前的许多报道表明,ATP7B 基因突变会导致铜转运 ATPase 2 蛋白缺陷,从而导致铜蓄积,引发威尔逊氏病:荟萃分析旨在全面掌握遗传变异的范围:根据 PRISMA 的指导原则进行了一项荟萃分析,旨在评估 ATP7B 基因突变的多样性和频率,重点是位于特定外显子内的突变:数据集中检测到的突变的位置、类型和命名法均来自以往的研究(时间跨度为 2013 年至 2023 年)。分析的重点是外显子特异性变异及其在不同人群中的流行率:共有 40 项研究纳入了当前的数据分析。我们的综合研究发现了多种突变,其中最显著的是超过50%的单核苷酸变化,分布在该基因的21个外显子上。其中以第 8 号外显子的突变最为多样,有 18 项研究发现了 53 个独特的变异,其中大部分是错义突变(81.13%)。此外,c.2333G>A/T(p.R778Q/L)、c.2305A>G(p.M769V)、c.2336G>A(p.W779*)和c.2304dupC(p.M769HfsX26)等变异在许多人群中都有报道。变异比例的加权平均值被用来计算这些百分比的集合估计值,c.2333G>A/T (p.R778Q/L) 为 14.19%,c.2305A>G (p.M769V) 为 2.70%,c.2336G>A (p.W779*) 为 1.42%,c.2304dupC (p.M769HfsX26) 为 2.33%:该设计展示了 ATP7B 基因的突变谱,尤其是第 8 号外显子,为了解第 8 号外显子突变的发生率和意义提供了重要依据。了解 ATP7B 基因突变有助于深入了解 WD 背后的机制,并为诊断和治疗策略提供指导。
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引用次数: 0
Decreased Serum Insulin Receptor Messenger RNA Level in H. pylori IgG Seropositive Type 2 Diabetic Patients. 幽门螺杆菌 IgG 血清阳性 2 型糖尿病患者血清胰岛素受体信使 RNA 水平降低
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241296619
Emmanuel Ayitey Tagoe, Jael Acquah Appiah, Pius Agyenim Boateng, Osbourne Quaye, Samuel Bosomprah

Background: Helicobacter pylori (H. pylori) is a known gastro-intestinal pathogen but implicated in extra-gastric diseases. The relationship between H. pylori infection and type 2 diabetes (T2DM) remains insufficiently elucidated, particularly in terms of molecular mediators such as microRNAs (miRNAs) and messenger RNAs (mRNAs).

Objective: We aimed to characterize expression pattern of insulin signalling mRNAs and targeted miRNAs in T2DM patients exposed to H. pylori infection.

Methods: We conducted a cross-sectional study among patients diagnosed with type 2 diabetes mellitus and were aged 18 to 60 years. Overnight fasting blood samples were collected and processed for plasma and serum. The plasma samples were used for glucose estimation and the serum used for H. pylori IgG screening. Total RNA was extracted from the serum with commercial kit, and mRNAs and miRNAs quantified by RT-qPCR with specific primers and under predetermined amplification conditions. Clinical data were obtained from medical records of patients.

Results: Among 351 patients enrolled, 267 (76.1%) were females, 224 (63.8%) were married, and 79 (22.5%) had tertiary education. Expression level of insulin receptor mRNA was significantly lower in H. pylori positive T2DM patients compared to H. pylori negative (P < .05). There was no evidence of a difference in insulin receptor substrate 1 mRNA level (P > .05). Although not statistically significant, the expression levels of miRNA-222 and miRNA-155 in the patients exposed to H. pylori were higher than that of the unexposed group (P > .05).

Conclusions: We found a significantly reduced serum insulin receptor messenger RNA level and higher levels of miRNA-222 and miRNA-155 in H. pylori exposed T2DM patients. The findings suggest a possible role of the infection in insulin signalling alteration in the patients.

背景:幽门螺杆菌(H. pylori)是一种已知的胃肠道病原体,但也与胃肠道以外的疾病有关。幽门螺杆菌感染与 2 型糖尿病(T2DM)之间的关系仍未得到充分阐明,尤其是在分子介质方面,如微小核糖核酸(miRNA)和信使核糖核酸(mRNA):我们的目的是描述幽门螺杆菌感染的 T2DM 患者中胰岛素信号 mRNA 和靶向 miRNA 的表达模式:我们对确诊为 2 型糖尿病的 18 至 60 岁患者进行了一项横断面研究。我们采集了隔夜空腹血样,并对血浆和血清进行了处理。血浆样本用于估算血糖,血清样本用于筛查幽门螺杆菌 IgG。使用商业试剂盒从血清中提取总 RNA,并在预定的扩增条件下使用特定引物通过 RT-qPCR 对 mRNA 和 miRNA 进行定量。临床数据来自患者的医疗记录:在 351 例患者中,267 例(76.1%)为女性,224 例(63.8%)已婚,79 例(22.5%)受过高等教育。幽门螺杆菌阳性 T2DM 患者的胰岛素受体 mRNA 表达水平明显低于幽门螺杆菌阴性患者(P P > .05)。暴露于幽门螺杆菌的患者中,miRNA-222和miRNA-155的表达水平高于未暴露组,但无统计学意义(P > .05):结论:我们发现暴露于幽门螺杆菌的 T2DM 患者血清胰岛素受体信使 RNA 水平明显降低,miRNA-222 和 miRNA-155 水平较高。这些研究结果表明,幽门螺杆菌感染可能会改变患者体内的胰岛素信号。
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引用次数: 0
The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells. 染色体乘客复合体(CPC)成分及其相关途径有望区分正常敏感细胞和辐射敏感的ATM突变细胞。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241274017
Anne Dietz, Prabal Subedi, Omid Azimzadeh, Lukas Duchrow, Felix Kaestle, Juliane Paetzold, Sarah Katharina Payer, Sabine Hornhardt, Christine von Toerne, Stefanie M Hauck, Bettina Kempkes, Cornelia Kuklik-Roos, Danielle Brandes, Arndt Borkhardt, Simone Moertl, Maria Gomolka

Background: Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutations in the ATM (mutated ataxia telangiectasia) gene, that cause the rare recessively inherited disease Ataxia telangiectasia (AT). Hallmark features include chromosomal instability and increased sensitivity to ionizing radiation (IR).

Objectives: To deepen the molecular understanding of radiosensitivity and to identify potential new markers to predict it, human ATM-mutated and proficient cells were compared on a proteomic level.

Design: In this study, we analyzed 3 cell lines from AT patients, with varying radiosensitivity, and 2 cell lines from healthy volunteers, 24 hours and 72 hours post-10 Gy irradiation.

Methods: We used label-free mass spectrometry to identify differences in signaling pathways after irradiation in normal and radiosensitive individuals. Cell viability was initially determined by water soluble tetrazolium (WST) assay and DNA damage response was analyzed with 53BP1 repair foci formation along with KRAB-associated protein 1 (KAP1) phosphorylation.

Results: Proteomic analysis identified 4028 proteins, which were used in subsequent in silico pathway enrichment analysis to predict affected biological pathways post-IR. In AT cells, networks were heterogeneous at both time points with no common pathway identified. Mitotic cell cycle progress was the most prominent pathway altered after IR in cells from healthy donors. In particular, components of the chromosome passenger complex (INCENP and CDCA8) were significantly downregulated after 72 hours. This could also be verified at the mRNA level.

Conclusion: Altogether, the most striking result was that proteins forming the chromosome passenger complex were downregulated after radiation exposure in healthy normosensitive control cells, but not in radiosensitive ATM-deficient cells. Thus, mitosis-associated proteins form an interesting compound to gain insights into the development and prediction of radiosensitivity.

背景:对电离辐射的敏感性因人而异,但人们对造成这些差异的生物机制了解有限。其中一个例子就是ATM(突变共济失调毛细血管扩张症)基因的突变,这种突变导致了罕见的隐性遗传疾病共济失调毛细血管扩张症(AT)。其特征包括染色体不稳定和对电离辐射(IR)的敏感性增加:为了加深对辐射敏感性的分子认识并确定预测辐射敏感性的潜在新标记,我们在蛋白质组水平上对人类ATM突变细胞和熟练细胞进行了比较:在这项研究中,我们分析了来自AT患者的3个细胞系(它们具有不同的辐射敏感性)和来自健康志愿者的2个细胞系(在10 Gy照射后24小时和72小时):方法:我们使用无标记质谱法来确定正常人和辐射敏感者接受辐照后信号通路的差异。通过水溶性四氮唑(WST)测定法初步确定细胞活力,并通过 53BP1 修复灶的形成和 KRAB 相关蛋白 1 (KAP1) 磷酸化分析 DNA 损伤反应:蛋白质组分析确定了 4028 个蛋白质,这些蛋白质被用于随后的硅通路富集分析,以预测感染 IR 后受影响的生物通路。在 AT 细胞中,两个时间点的网络都是异质的,没有发现共同的通路。在健康供体的细胞中,有丝分裂细胞周期进展是红外照射后发生改变的最主要途径。特别是,染色体客体复合物(INCENP 和 CDCA8)的成分在 72 小时后显著下调。这也可以在 mRNA 水平上得到验证:总之,最引人注目的结果是,在健康的正常敏感对照细胞中,形成染色体乘客复合体的蛋白质在辐照后下调,而在辐射敏感的ATM缺陷细胞中则没有。因此,有丝分裂相关蛋白是一种有趣的化合物,有助于深入了解辐射敏感性的发展和预测。
{"title":"The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells.","authors":"Anne Dietz, Prabal Subedi, Omid Azimzadeh, Lukas Duchrow, Felix Kaestle, Juliane Paetzold, Sarah Katharina Payer, Sabine Hornhardt, Christine von Toerne, Stefanie M Hauck, Bettina Kempkes, Cornelia Kuklik-Roos, Danielle Brandes, Arndt Borkhardt, Simone Moertl, Maria Gomolka","doi":"10.1177/11772719241274017","DOIUrl":"10.1177/11772719241274017","url":null,"abstract":"<p><strong>Background: </strong>Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutations in the ATM (mutated ataxia telangiectasia) gene, that cause the rare recessively inherited disease Ataxia telangiectasia (AT). Hallmark features include chromosomal instability and increased sensitivity to ionizing radiation (IR).</p><p><strong>Objectives: </strong>To deepen the molecular understanding of radiosensitivity and to identify potential new markers to predict it, human ATM-mutated and proficient cells were compared on a proteomic level.</p><p><strong>Design: </strong>In this study, we analyzed 3 cell lines from AT patients, with varying radiosensitivity, and 2 cell lines from healthy volunteers, 24 hours and 72 hours post-10 Gy irradiation.</p><p><strong>Methods: </strong>We used label-free mass spectrometry to identify differences in signaling pathways after irradiation in normal and radiosensitive individuals. Cell viability was initially determined by water soluble tetrazolium (WST) assay and DNA damage response was analyzed with 53BP1 repair foci formation along with KRAB-associated protein 1 (KAP1) phosphorylation.</p><p><strong>Results: </strong>Proteomic analysis identified 4028 proteins, which were used in subsequent in silico pathway enrichment analysis to predict affected biological pathways post-IR. In AT cells, networks were heterogeneous at both time points with no common pathway identified. Mitotic cell cycle progress was the most prominent pathway altered after IR in cells from healthy donors. In particular, components of the chromosome passenger complex (INCENP and CDCA8) were significantly downregulated after 72 hours. This could also be verified at the mRNA level.</p><p><strong>Conclusion: </strong>Altogether, the most striking result was that proteins forming the chromosome passenger complex were downregulated after radiation exposure in healthy normosensitive control cells, but not in radiosensitive ATM-deficient cells. Thus, mitosis-associated proteins form an interesting compound to gain insights into the development and prediction of radiosensitivity.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241274017"},"PeriodicalIF":3.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
D-dimer as a Predictive Biomarker of Response to Chemotherapy in Patients With Metastatic Breast Cancer. D-二聚体作为转移性乳腺癌患者化疗反应的预测性生物标记物
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-17 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241290704
Lubana Alkhoder, Maher Salamoon, Maher Saifo, Sulaf Alwassouf

Background: Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types.

Objectives: This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients.

Design: This was a prospective study.

Methods: This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy.

Results: In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer.

Conclusion: D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.

背景:肿瘤诱导凝血在癌症患者中广泛存在。此外,肿瘤诱导凝血与肿瘤发生、肿瘤进展和转移有关,因为它创造了一个增殖和促血管生成的微环境。因此,纤维蛋白降解产物 D-二聚体与多种癌症类型的肿瘤预后相关:本研究旨在探讨 D-二聚体水平是否可作为转移性乳腺癌(MBC)患者化疗反应的预测和监测指标:设计:这是一项前瞻性研究:本研究包括两组患者,分别是76名确诊为转移性乳腺癌的患者和25名原发性乳腺癌患者。在开始化疗前和第四个治疗周期后,对 MBC 患者的血浆 D-二聚体水平进行前瞻性测量。使用接收者操作特征曲线(ROC)分析化疗前(D0)的D-二聚体水平,以确定D0的最佳临界基线值,并评估其预测化疗反应的判别能力:在初步反应评估中,部分反应模式患者的 D-二聚体平均水平明显下降了 0.65 μg/ml,病情稳定患者的 D-二聚体平均水平下降了 0.5 μg/ml。在疾病进展组中,D-二聚体水平明显增加了 1.2 μg/ml。ROC曲线分析表明,D0时的D-二聚体水平可判别对化疗的反应,而疾病进展率与较高的D-二聚体水平相关:结论:血浆中的D-二聚体水平是预测和监测转移性乳腺癌化疗反应的有效指标。
{"title":"D-dimer as a Predictive Biomarker of Response to Chemotherapy in Patients With Metastatic Breast Cancer.","authors":"Lubana Alkhoder, Maher Salamoon, Maher Saifo, Sulaf Alwassouf","doi":"10.1177/11772719241290704","DOIUrl":"10.1177/11772719241290704","url":null,"abstract":"<p><strong>Background: </strong>Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types.</p><p><strong>Objectives: </strong>This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients.</p><p><strong>Design: </strong>This was a prospective study.</p><p><strong>Methods: </strong>This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy.</p><p><strong>Results: </strong>In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer.</p><p><strong>Conclusion: </strong>D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241290704"},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer. 生物标志物从发现到临床应用:面对肺癌的硅学临床前验证方法。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241287400
Medi Kori, Esra Gov, Kazim Yalcin Arga, Raghu Sinha

Background: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application.

Objective: Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment.

Design: As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach.

Methods: We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs.

Results: We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively.

Conclusion: In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research.

背景:临床生物标志物可根据疾病风险、预后和/或对治疗的反应对患者进行更好的分类。尽管价格低廉的基于组学的方法为更快地确定推定生物标志物铺平了道路,但生物标志物的验证是将发现转化为临床应用的必要条件:因此,在本研究中,我们强调了硅学方法的潜力,并提出和应用了 3 个新颖的硅学临床前验证步骤,以更好地确定真正适合临床投资的生物标志物:由于蛋白质生物标记物与其他分子生物标记物在临床中的重要性日益增加,而肺癌是癌症相关死亡的最常见原因,因此我们以肺癌蛋白质生物标记物为例来应用我们的硅学临床前验证方法:我们收集了3个病例(肺腺癌-LUAD、鳞状细胞癌-LUSC和未指定肺癌)中报告的蛋白质生物标志物,并评估了这些蛋白质生物标志物是否具有改变癌症的特性(即作为肿瘤抑制因子或肿瘤蛋白,代表癌症标志物),是否在体液中表达,以及是否可以被FDA批准的药物靶向:我们收集了 3008 个肺癌蛋白质生物标记物、1189 个 LUAD 蛋白标记物和 182 个 LUSC 蛋白标记物。在这些肺癌、LUAD 和 LUSC 蛋白质生物标记物中,分别只有 28、25 和 6 个蛋白质生物标记物通过了 3 个硅学临床前验证步骤,其中分别只有 5 和 2 个生物标记物对肺癌和 LUAD 具有特异性:在这项研究中,我们采用了硅学临床前验证方法对肺癌病例的蛋白质生物标志物进行了验证。不过,这种方法也可应用于所有癌症生物标志物。我们相信,这种方法将极大地促进癌症生物标志物进入临床阶段,并为未来的生物标志物研究提供巨大的潜力。
{"title":"Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer.","authors":"Medi Kori, Esra Gov, Kazim Yalcin Arga, Raghu Sinha","doi":"10.1177/11772719241287400","DOIUrl":"10.1177/11772719241287400","url":null,"abstract":"<p><strong>Background: </strong>Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application.</p><p><strong>Objective: </strong>Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment.</p><p><strong>Design: </strong>As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach.</p><p><strong>Methods: </strong>We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs.</p><p><strong>Results: </strong>We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively.</p><p><strong>Conclusion: </strong>In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241287400"},"PeriodicalIF":3.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Correlation Between Hypoxia, HIF1A Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis. 通过酶联免疫吸附试验和综合多组学分析探讨不同种族和孟加拉妇女缺氧、HIF1A 变异与乳腺癌之间的相关性:通过 ELISA 和综合多指标分析。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241278176
Md Shihabul Islam, Jesmin

Background: Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression.

Objective: This study investigates the correlation between HIF1A gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets.

Design: This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer.

Method: This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis.

Results: In Bangladeshi BC cases, the T allele of HIF1A rs1154946 correlates notably (P-value < .001) with BC incidence. ELISA results confirmed a significant association (P-value < .005) between elevated HIF1A expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased HIF1A expression and rs11549465 T allele (P-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting HIF1A function. HIF1A enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (P-value < .001). Transcriptomic data demonstrated a robust correlation (P-value < .0001) between HIF1A expression and copy-number alterations, mutations, and abnormal methylation. Altered HIF1A expression showed strong negative correlations (P-value < .00001) with methylation and the expression of the ER (ESR1), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low HIF1A expression (P-value < .00001). Furthermore, HIF1A expression significantly correlated (P-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment.

Conclusion: Thus, the HIF1A gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.

背景:缺氧是一种缺氧状态,已知在癌症进展过程中起作用:本研究调查了孟加拉国乳腺癌(BC)病例和 TCGA_BC 数据集中 HIF1A 基因表达改变与缺氧之间的相关性:这项病例对照研究将孟加拉乳腺癌病例与健康对照进行比较,以了解基因变化与癌症之间的关系:本研究采用先进的分析方法研究了孟加拉国乳腺癌的转录格局,并利用多组学综合分析方法对其相关性进行了定量评估:结果:在孟加拉国的BC病例中,HIF1A rs1154946的T等位基因与BC相关缺氧显著相关(P-value P-value HIF1A表达)。生物信息学 eQTL 分析验证了 HIF1A 表达增加与 rs11549465 T 等位基因的相关性(P-value HIF1A 功能)。对 BC 中 HIF1A 的富集分析表明,HIF1A 与氧水平、缺氧、代谢过程、细胞凋亡和程序性细胞死亡密切相关(P-value HIF1A 表达与拷贝数改变、突变和异常甲基化有关。在白人中,HIF1A表达的改变显示出强烈的负相关(P值ESR1)。生存分析表明,HIF1A 高表达和低表达在总生存率上存在明显差异(P-value HIF1A 表达显著相关(P-value 结论):因此,HIF1A 基因可作为乳腺癌进展、控制和跨种族生存的有前途的生物标记物,强调其在疾病发展和调节中的作用。
{"title":"Exploring the Correlation Between Hypoxia, <i>HIF1A</i> Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis.","authors":"Md Shihabul Islam, Jesmin","doi":"10.1177/11772719241278176","DOIUrl":"10.1177/11772719241278176","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression.</p><p><strong>Objective: </strong>This study investigates the correlation between <i>HIF1A</i> gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets.</p><p><strong>Design: </strong>This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer.</p><p><strong>Method: </strong>This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis.</p><p><strong>Results: </strong>In Bangladeshi BC cases, the T allele of <i>HIF1A</i> rs1154946 correlates notably (<i>P</i>-value < .001) with BC incidence. ELISA results confirmed a significant association (<i>P</i>-value < .005) between elevated <i>HIF1A</i> expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased <i>HIF1A</i> expression and rs11549465 T allele (<i>P</i>-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting <i>HIF1A</i> function. <i>HIF1A</i> enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (<i>P</i>-value < .001). Transcriptomic data demonstrated a robust correlation (<i>P</i>-value < .0001) between <i>HIF1A</i> expression and copy-number alterations, mutations, and abnormal methylation. Altered <i>HIF1A</i> expression showed strong negative correlations (<i>P</i>-value < .00001) with methylation and the expression of the ER (<i>ESR1</i>), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low <i>HIF1A</i> expression (<i>P</i>-value < .00001). Furthermore, <i>HIF1A</i> expression significantly correlated (<i>P</i>-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment.</p><p><strong>Conclusion: </strong>Thus, the <i>HIF1A</i> gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241278176"},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correlation Analyses Between Serum Interleukin-7, Interleukin-15 and Lactate Provide Insights Into Their Potential Roles in the Regulation of Inflammation in Elderly Septic Patients. 血清白细胞介素-7、白细胞介素-15 和乳酸盐之间的相关性分析有助于了解它们在老年败血症患者炎症调节中的潜在作用。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-09 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241275525
Jingjing Zhao, Ye Zhang, Jun-Yu Wang, Bing Wei, Yu-Geng Liu

Background: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients.

Objectives: This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients.

Design: This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.

Methods: The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed.

Results: Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group (P < .05). Correlations between serum levels of IL-7 and platelet-derived growth factor-AA (PDGF-AA), as well as correlations between IL-15, IL-6, and TNF-α were confirmed (P < .05). Both the serum levels of lactate and IL-15 correlated with the total counts of platelet (PLT) in the survival subgroup with low APACHE Ⅱ scores while the serum levels of IL-7, IL-15, and total counts of monocytes correlated with each other in the nonsurvival subgroup with different APACHE Ⅱ scores (P < .05).

Conclusion: Knowledge of the regulation networks between serum levels of IL-7, IL-15, lactate, and other cytokines may provide insights into potential mechanisms in the modulation of inflammation in elderly septic patients and facilitate more prompt and accurate treatment to reduce the mortality rate.

背景:我们之前的研究发现白细胞介素(IL)-7和IL-15是老年脓毒症患者的预后生物标志物,然而,人们对老年脓毒症患者血清中IL-7、IL-15和乳酸盐水平之间的联系以及它们在炎症调节中的潜在作用知之甚少:本研究旨在探讨老年脓毒症患者血清中 IL-7、IL-15 和乳酸盐水平之间的联系以及与其他因素的关系:这是一项回顾性研究,共纳入 129 名老年脓毒症患者,分为存活组(34 人)和非存活组(95 人),并根据急性生理学和慢性健康评估 II(APACHE II)评分进一步分组:入院后 24 小时内记录基线数据和临床参数。采用 Luminex 检测法对血清中的细胞因子水平进行量化。结果结果:非存活组的血清中 IL-6、IL-7、IL-15 和肿瘤坏死因子-α(TNF-α)的水平显著高于存活组(P P P 结论:血清中细胞因子之间的调控网络是影响存活组的重要因素:了解血清中IL-7、IL-15、乳酸和其他细胞因子水平之间的调控网络,有助于了解老年脓毒症患者炎症调节的潜在机制,并促进更及时、准确的治疗,降低死亡率。
{"title":"Correlation Analyses Between Serum Interleukin-7, Interleukin-15 and Lactate Provide Insights Into Their Potential Roles in the Regulation of Inflammation in Elderly Septic Patients.","authors":"Jingjing Zhao, Ye Zhang, Jun-Yu Wang, Bing Wei, Yu-Geng Liu","doi":"10.1177/11772719241275525","DOIUrl":"https://doi.org/10.1177/11772719241275525","url":null,"abstract":"<p><strong>Background: </strong>Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients.</p><p><strong>Objectives: </strong>This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients.</p><p><strong>Design: </strong>This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.</p><p><strong>Methods: </strong>The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed.</p><p><strong>Results: </strong>Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group (<i>P</i> < .05). Correlations between serum levels of IL-7 and platelet-derived growth factor-AA (PDGF-AA), as well as correlations between IL-15, IL-6, and TNF-α were confirmed (<i>P</i> < .05). Both the serum levels of lactate and IL-15 correlated with the total counts of platelet (PLT) in the survival subgroup with low APACHE Ⅱ scores while the serum levels of IL-7, IL-15, and total counts of monocytes correlated with each other in the nonsurvival subgroup with different APACHE Ⅱ scores (<i>P</i> < .05).</p><p><strong>Conclusion: </strong>Knowledge of the regulation networks between serum levels of IL-7, IL-15, lactate, and other cytokines may provide insights into potential mechanisms in the modulation of inflammation in elderly septic patients and facilitate more prompt and accurate treatment to reduce the mortality rate.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241275525"},"PeriodicalIF":3.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of RNA Processing Genes in Colon Cancer for Predicting Clinical Outcomes. 表征结肠癌中的 RNA 处理基因,预测临床结果。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-08-18 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241258642
Jianwen Hu, Yingze Ning, Yongchen Ma, Lie Sun, Guowei Chen

Objective: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated.

Methods: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features.

Results: An RNA processing-related prognostic risk model based on 10 genes including FXR1, MFAP1, RBM17, SAGE1, SNRPA1, SRRM4, ADAD1, DDX52, ERI1, and EXOSC7 was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8+ T cells and poorer clinical prognosis than the low-risk group.

Conclusion: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.

目的:结肠癌具有多层次的分子异质性。RNA 加工将初级转录 RNA 转化为成熟 RNA,从而推动肿瘤的发生和维持。结肠癌中 RNA 加工基因的特征亟待阐明:本研究从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达总库(Gene Expression Omnibus,GEO)数据库中获取了 1033 个相关样本,以探索结肠癌中 RNA 处理表型的异质性。首先,无监督分层聚类分析通过分析 485 个 RNA 处理基因,发现了具有特定临床结果和生物学特征的 4 个亚型。接着,我们采用最小绝对收缩和选择算子(LASSO)以及带惩罚的考克斯回归模型来描述与RNA加工相关的预后特征:结果:最终确定了基于 10 个基因的 RNA 处理相关预后风险模型,包括 FXR1、MFAP1、RBM17、SAGE1、SNRPA1、SRRM4、ADAD1、DDX52、ERI1 和 EXOSC7。通过将这一特征与其余临床变量(包括 TNM、年龄、性别和分期)相结合,构建了综合预后提名图。此外,还通过生物信息学方法分析了风险特征的遗传变异、通路激活和免疫异质性。结果表明,与低风险组相比,高风险亚组与较高的基因组不稳定性、增殖和周期特征增加、肿瘤杀伤CD8+ T细胞减少以及较差的临床预后有关:结论:这种基于 RNA 编辑基因的预后分类器有助于根据 TNM 和临床结果、基因变异、通路激活和免疫异质性将结肠癌分为特定的亚组。它可用于诊断、分类和靶向治疗策略,与目前的精准医学标准相当。它为阐明 RNA 编辑基因作为预后标志物在结肠癌中的作用及其临床意义提供了理论依据。
{"title":"Characterization of RNA Processing Genes in Colon Cancer for Predicting Clinical Outcomes.","authors":"Jianwen Hu, Yingze Ning, Yongchen Ma, Lie Sun, Guowei Chen","doi":"10.1177/11772719241258642","DOIUrl":"10.1177/11772719241258642","url":null,"abstract":"<p><strong>Objective: </strong>Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated.</p><p><strong>Methods: </strong>In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features.</p><p><strong>Results: </strong>An RNA processing-related prognostic risk model based on 10 genes including <i>FXR1</i>, <i>MFAP1</i>, <i>RBM17</i>, <i>SAGE1</i>, <i>SNRPA1</i>, <i>SRRM4</i>, <i>ADAD1</i>, <i>DDX52</i>, <i>ERI1</i>, and <i>EXOSC7</i> was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8<sup>+</sup> T cells and poorer clinical prognosis than the low-risk group.</p><p><strong>Conclusion: </strong>This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241258642"},"PeriodicalIF":3.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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