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The causal nexus between diverse smoking statuses, potential therapeutic targets, and NSCLC: insights from Mendelian randomization and mediation analysis. 不同吸烟状况、潜在治疗靶点和 NSCLC 之间的因果关系:孟德尔随机化和中介分析的启示。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1438851
Zhenghua Cao, Shengkun Zhao, Tong Wu, Huan Ding, Zhiyu Tian, Feng Sun, Zhuo Feng, Shaodan Hu, Li Shi

Objective: Lung cancer, the most prevalent malignancy, is typically diagnosed at an advanced stage. Smoking is a pivotal risk factor for NSCLC, yet the impact of various smoking statuses on NSCLC remains unclear. Thus, this study aims to explore whether different smoking statuses can causally influence NSCLC through effects on predictive targets, offering a novel perspective for NSCLC treatment.

Methods: Employing dual-sample MR, MVMR, and TSMR approaches, we assessed the causal relationships between 13 distinct smoking statuses and NSCLC, using predicted potential therapeutic targets as mediators to further elucidate the causal interplay among them.

Results: Among the 13 smoking statuses, current tobacco smoking, exposure to tobacco smoke outside the home, past tobacco smoking, and never smoked demonstrated causal relationships with NSCLC. MVMR analysis reveals that Current tobacco smoking is an independent risk factor for NSCLC. Utilizing NCAPD2, IL11RA, and MLC1 as mediators, IL11RA (22.2%) was found to potentially mediate the relationship between past tobacco smoking and NSCLC.

Conclusion: This study, integrating bioinformatics and MR analysis, identified three potential predictive targets as mediators to investigate the causal relationships between different smoking statuses and NSCLC through potential therapeutic targets, providing new insights for the treatment and prevention of NSCLC.

目的:肺癌是发病率最高的恶性肿瘤,通常在确诊时已是晚期。吸烟是导致 NSCLC 的关键风险因素,但各种吸烟状态对 NSCLC 的影响仍不清楚。因此,本研究旨在探讨不同的吸烟状态是否会通过对预测靶点的影响而对 NSCLC 产生因果影响,从而为 NSCLC 的治疗提供新的视角:方法:我们采用双样本 MR、MVMR 和 TSMR 方法,评估了 13 种不同吸烟状态与 NSCLC 之间的因果关系,并以预测的潜在治疗靶点为中介,进一步阐明了它们之间的因果相互作用:结果:在 13 种吸烟状态中,当前吸烟、暴露于家庭外烟草烟雾、过去吸烟和从不吸烟与 NSCLC 存在因果关系。MVMR分析显示,当前吸烟是NSCLC的独立风险因素。利用 NCAPD2、IL11RA 和 MLC1 作为中介因子,发现 IL11RA(22.2%)可能是过去吸烟与 NSCLC 关系的中介因子:本研究结合生物信息学和磁共振分析,确定了三个潜在的预测靶点作为中介因子,通过潜在的治疗靶点研究不同吸烟状况与 NSCLC 之间的因果关系,为治疗和预防 NSCLC 提供了新的见解。
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引用次数: 0
Therapeutic strategies to overcome ALK-fusion and BRAF-mutation as acquired resistance mechanism in EGFR-mutated non-small cell lung cancer: two case reports. 克服作为表皮生长因子受体突变非小细胞肺癌获得性耐药机制的 ALK 融合和 BRAF 突变的治疗策略:两个病例报告。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1390523
Yuan Zeng, Qiang Zeng, Bin Yang, Yang Hu

Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. EGFR tyrosine inhibitors are the preferred first-line treatment for patients with epidermal growth factor-cell receptor mutant (EGFR mutant) advanced NSCLC. Unfortunately, drug resistance inevitably occurs leading to disease progression. Activation of the ALK and BRAF bypass signaling pathways is a rare cause of acquired drug resistance for EGFR-TKIs.We report two NSCLC-patients with EGFR- mutations, in exon 19, and exon 18, correspondingly, who were treated with EGFR-TKIs. The first case shows acquired BRAF-mutation, and the second case demonstrates acquired ALK-fusion. The overall survival of patients was significantly prolonged by drug-match therapies. As it is well-known that ALK-fusion and BRAF-mutations are described forms of acquired resistance. These two case reports contribute to the previous reports that ALK-fusion and BRAF-mutation are potential underlying mechanisms of EGFR-TKI resistance.

非小细胞肺癌(NSCLC)是世界上最常见的恶性肿瘤之一。表皮生长因子受体酪氨酸抑制剂是表皮生长因子细胞受体突变(表皮生长因子受体突变)晚期非小细胞肺癌患者的首选一线治疗药物。不幸的是,耐药性的出现不可避免地会导致疾病进展。ALK和BRAF旁路信号通路的激活是导致表皮生长因子受体抑制剂获得性耐药的罕见原因。我们报告了两名表皮生长因子受体19号外显子和18号外显子发生突变的NSCLC患者,他们分别接受了表皮生长因子受体抑制剂治疗。第一个病例显示获得性 BRAF 突变,第二个病例显示获得性 ALK 融合。通过药物匹配疗法,患者的总生存期明显延长。众所周知,ALK融合和BRAF突变是获得性耐药的描述形式。这两份病例报告进一步证实,ALK融合和BRAF突变是表皮生长因子受体-TKI耐药的潜在机制。
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引用次数: 0
Editorial: Critical complications in pediatric oncology and hematopoietic cell transplant, volume II. 社论:儿科肿瘤学和造血细胞移植中的严重并发症,第二卷。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1512659
Jennifer Ann McArthur, Kris M Mahadeo, Asya Agulnik, Marie E Steiner
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引用次数: 0
Exercise's impact on lung cancer molecular mechanisms: a current overview. 运动对肺癌分子机制的影响:当前概述。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1479454
Annamaria Mancini, Francesca Maria Orlandella, Daniela Vitucci, Neila Luciano, Andreina Alfieri, Stefania Orrù, Giuliana Salvatore, Pasqualina Buono

Lung cancer is the major cause of cancer-related deaths worldwide with an estimated 1.8 million deaths and 2.4 million new cases in 2022. Poor cardiorespiratory fitness, dyspnea and fatigue are the common features in lung cancer patients, partially limiting the exercise prescription. Exercise improves cardiorespiratory and muscular fitness and reduces the risk of some types of cancer, including lung cancer. Recently, the American Society of Clinical Oncology has encouraged preoperative exercise for lung cancer patients. Nonetheless, only limited data, mostly obtained from mouse models of lung cancer, are available on the molecular effects of exercise in lung cancer. Thus, the present minireview aims to shed light on the molecular mechanisms induced by different type of exercise in lung cancer. In particular, the role of the exercise in tumor microenvironment remodeling, angiogenesis, gene expression, apoptosis and intermediate metabolism will be examined.

肺癌是全球癌症相关死亡的主要原因,预计 2022 年将有 180 万人死于肺癌,新增病例 240 万。心肺功能差、呼吸困难和疲劳是肺癌患者的共同特征,这在一定程度上限制了运动处方。运动可改善心肺功能和肌肉健康,降低包括肺癌在内的某些类型癌症的患病风险。最近,美国临床肿瘤学会鼓励肺癌患者进行术前锻炼。然而,关于运动对肺癌的分子影响,目前只有有限的数据,大部分数据来自肺癌小鼠模型。因此,本小节旨在阐明不同类型的运动对肺癌的分子机制。特别是将研究运动在肿瘤微环境重塑、血管生成、基因表达、细胞凋亡和中间代谢中的作用。
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引用次数: 0
The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study. 肿瘤负荷评分对肝细胞癌根治性切除术后患者预后的影响:一项单中心回顾性研究。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1359017
Junzhang Huang, Ying Zhou, Suosu Wei, Yuntian Tang, Qiuhuan Zhang, Yi Tang, Wei Huang, Chongde Mo, Xiaofeng Dong, Jianrong Yang

Purpose: This study examines the relationship between tumor burden score (TBS) and survival and recurrence following radical resection of hepatocellular carcinoma through a cohort study conducted in the Guangxi population of China.

Methods: This cohort study eventually recruited 576 HCC patients undergoing radical resection of HCC in the People's Hospital of Guangxi Zhuang Autonomous Region during 2013-2022. After determining the best threshold TBS, all cases were grouped to evaluate the relationship between TBS versus overall survival (OS) and cumulative recurrence. Using X-Tile software, the best threshold TBS to judge patient prognostic outcome following radical resection of HCC was 10.77.

Results: Kaplan-Meier curve analysis revealed that patients with high TBS showed considerably decreased OS relative to the control group, accompanied by an increased recurrence rate. According to multivariate Cox proportional regression, the patients with high TBS were associated with poorer OS (HR = 2.56, 95% CI 1.64-3.99, P < 0.001) and recurrence-free survival (RFS) (HR = 1.55, 95% CI 1.02-2.35, P < 0.001).

Conclusion: In patients undergoing radical resection for HCC, higher TBS was significantly related to shorter OS and RFS.

目的:本研究通过在中国广西人群中开展队列研究,探讨肿瘤负荷评分(TBS)与肝细胞癌根治性切除术后生存和复发之间的关系:该队列研究最终招募了2013-2022年间在广西壮族自治区人民医院接受肝癌根治性切除术的576例HCC患者。在确定最佳阈值TBS后,对所有病例进行分组,评估TBS与总生存率(OS)和累积复发率之间的关系。利用X-Tile软件,判断HCC根治性切除术后患者预后的最佳阈值TBS为10.77:Kaplan-Meier曲线分析显示,与对照组相比,高TBS患者的OS明显下降,同时复发率增加。多变量考克斯比例回归显示,高TBS患者的OS(HR = 2.56,95% CI 1.64-3.99,P < 0.001)和无复发生存期(RFS)(HR = 1.55,95% CI 1.02-2.35,P < 0.001)均较差:结论:在接受HCC根治性切除术的患者中,TBS越高,OS和RFS越短。
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引用次数: 0
Thematic trends and knowledge-map of tumor-infiltrating lymphocytes in breast cancer: a scientometric analysis. 乳腺癌中肿瘤浸润淋巴细胞的主题趋势和知识图谱:科学计量分析。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1438091
Jinan Shi, Lei Pan, Feixia Ma, Ganlu Zhang, Yin Duan

Background: Tumor-infiltrating lymphocytes (TILs), essential for the anti-tumor response, are now recognized as promising and cost-effective biomarkers with both prognostic and predictive value. They are crucial in the precision treatment of breast cancer, particularly for predicting clinical outcomes and identifying candidates for immunotherapy. This study aims to encapsulate the current knowledge of TILs in breast cancer research while evaluating research trends both qualitatively and quantitatively.

Methods: Publications on TILs in breast cancer studies from January 1, 2004, to December 31, 2023, were extracted from the Web of Science Core Collection. Co-occurrence and collaboration analyses among countries/regions, institutions, authors, and keywords were performed with Bibliometrix R packages and VOSviewer software. CiteSpace was used for reference and keyword burst detection, while high-frequency keyword layouts were generated using BICOMB. gCLUTO was employed for biclustering analysis of the binary co-keyword matrix.

Results: A total of 2,066 articles on TILs in breast cancer were identified. Between 2004 and 2023, the USA and Milan University led productivity in terms of country/region and institution, respectively. The journals "CANCERS," "Breast Cancer Research and Treatment," and "Frontiers in Oncology" published the most articles on this topic. Loi S was the leading author, with the highest number of publications and co-citations. Co-keyword analysis revealed six research hotspots related to TILs in breast cancer. The pathological assessment of TILs using artificial intelligence (AI) remains in its early stages but is a key focus. Burst detection of keywords indicated significant activity in "immune cell infiltration", "immune checkpoint inhibitors", and "hormone receptor" over the past three years.

Conclusion: This study reviews recent advancements and trends in TILs research in breast cancer using scientometric analysis. The findings offer valuable insights for funding decisions and developing innovative strategies in TILs research, highlighting current research frontiers and trends.

背景:肿瘤浸润淋巴细胞(TILs)对抗肿瘤反应至关重要,目前已被公认为具有预后和预测价值、前景广阔且经济有效的生物标志物。它们对乳腺癌的精准治疗至关重要,尤其是在预测临床结果和确定免疫疗法候选者方面。本研究旨在总结目前乳腺癌研究中有关TILs的知识,同时对研究趋势进行定性和定量评估:方法:从 Web of Science 核心文献集中提取了 2004 年 1 月 1 日至 2023 年 12 月 31 日期间有关乳腺癌研究中 TILs 的文献。使用 Bibliometrix R 软件包和 VOSviewer 软件对国家/地区、机构、作者和关键词之间的共现和合作进行分析。CiteSpace 用于参考文献和关键词突发检测,而高频关键词布局则使用 BICOMB 生成,gCLUTO 用于二元共关键词矩阵的双聚分析:结果:共发现 2,066 篇关于乳腺癌中 TILs 的文章。从 2004 年到 2023 年,美国和米兰大学分别在国家/地区和机构方面居于领先地位。CANCERS》、《Breast Cancer Research and Treatment》和《Frontiers in Oncology》等期刊发表了最多有关这一主题的文章。Loi S是主要作者,发表文章和共同引用次数最多。共关键词分析揭示了与乳腺癌中的TILs相关的六个研究热点。利用人工智能(AI)对TILs进行病理评估仍处于早期阶段,但已成为研究重点。关键词的突发性检测表明,在过去三年中,"免疫细胞浸润"、"免疫检查点抑制剂 "和 "激素受体 "方面的研究十分活跃:本研究利用科学计量分析回顾了乳腺癌 TILs 研究的最新进展和趋势。研究结果为 TILs 研究的资助决策和创新战略的制定提供了有价值的见解,突出了当前的研究前沿和趋势。
{"title":"Thematic trends and knowledge-map of tumor-infiltrating lymphocytes in breast cancer: a scientometric analysis.","authors":"Jinan Shi, Lei Pan, Feixia Ma, Ganlu Zhang, Yin Duan","doi":"10.3389/fonc.2024.1438091","DOIUrl":"10.3389/fonc.2024.1438091","url":null,"abstract":"<p><strong>Background: </strong>Tumor-infiltrating lymphocytes (TILs), essential for the anti-tumor response, are now recognized as promising and cost-effective biomarkers with both prognostic and predictive value. They are crucial in the precision treatment of breast cancer, particularly for predicting clinical outcomes and identifying candidates for immunotherapy. This study aims to encapsulate the current knowledge of TILs in breast cancer research while evaluating research trends both qualitatively and quantitatively.</p><p><strong>Methods: </strong>Publications on TILs in breast cancer studies from January 1, 2004, to December 31, 2023, were extracted from the Web of Science Core Collection. Co-occurrence and collaboration analyses among countries/regions, institutions, authors, and keywords were performed with Bibliometrix R packages and VOSviewer software. CiteSpace was used for reference and keyword burst detection, while high-frequency keyword layouts were generated using BICOMB. gCLUTO was employed for biclustering analysis of the binary co-keyword matrix.</p><p><strong>Results: </strong>A total of 2,066 articles on TILs in breast cancer were identified. Between 2004 and 2023, the USA and Milan University led productivity in terms of country/region and institution, respectively. The journals \"CANCERS,\" \"Breast Cancer Research and Treatment,\" and \"Frontiers in Oncology\" published the most articles on this topic. Loi S was the leading author, with the highest number of publications and co-citations. Co-keyword analysis revealed six research hotspots related to TILs in breast cancer. The pathological assessment of TILs using artificial intelligence (AI) remains in its early stages but is a key focus. Burst detection of keywords indicated significant activity in \"immune cell infiltration\", \"immune checkpoint inhibitors\", and \"hormone receptor\" over the past three years.</p><p><strong>Conclusion: </strong>This study reviews recent advancements and trends in TILs research in breast cancer using scientometric analysis. The findings offer valuable insights for funding decisions and developing innovative strategies in TILs research, highlighting current research frontiers and trends.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"14 ","pages":"1438091"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of systemic immune-inflammation index in predicting pathological complete response of breast cancer after neoadjuvant therapy and the establishment of related predictive model. 全身免疫炎症指数在预测乳腺癌新辅助治疗后病理完全反应中的作用及相关预测模型的建立
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1437140
Ziyue Zhang, Yixuan Zeng, Wenbo Liu

Objective: To investigate the role of systemic immune-inflammation index (SII) in complete pathological response (pCR) of breast cancer patients after neoadjuvant chemotherapy, and to establish and validate a nomogram for predicting pCR.

Methods: Breast cancer patients were selected from the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2023. The optimal cut-off value of SII was calculated via ROC curve. The correlation between SII and clinicopathological characteristics was analyzed by Chi-square test. Logistic regression analysis was performed to evaluate the factors that might affect pCR. Based on the results of Logistic regression analysis, a nomogram for predicting pCR was established and validated.

Results: A total of 112 breast cancer patients were included in this study. 33.04% of the patients achieved pCR after neoadjuvant therapy. Chi-square test showed that SII was significantly correlated with pCR (P=0.001). Logistic regression analysis suggested that Ki-67 (P=0.039), therapy cycle (P<0.001), CEA (P=0.025) and SII (P=0.019) were independent predictors of pCR after neoadjuvant chemotherapy. A nomogram based on Ki-67, therapy cycle, CEA and SII showed a good predictive ability.

Conclusion: Ki-67, therapy cycle, CEA and SII were independent predictors of pCR of breast cancer after neoadjuvant chemotherapy. The nomogram based on the above positive factors showed a good predictive ability.

目的研究全身免疫炎症指数(SII)在新辅助化疗后乳腺癌患者完全病理反应(pCR)中的作用,并建立和验证预测pCR的提名图:方法:选取西安交通大学第一附属医院2020年1月至2023年12月的乳腺癌患者作为研究对象。通过 ROC 曲线计算出 SII 的最佳临界值。通过Chi-square检验分析SII与临床病理特征的相关性。为评估可能影响 pCR 的因素,进行了 Logistic 回归分析。根据 Logistic 回归分析的结果,建立并验证了预测 pCR 的提名图:本研究共纳入了 112 名乳腺癌患者。33.04%的患者在接受新辅助治疗后获得了pCR。卡方检验显示,SII与pCR显著相关(P=0.001)。逻辑回归分析表明,Ki-67(P=0.039)、治疗周期(PConclusion:Ki-67、治疗周期、CEA和SII是新辅助化疗后乳腺癌pCR的独立预测指标。基于上述阳性因子的提名图显示了良好的预测能力。
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引用次数: 0
Case report: Patient-derived organoids promoting personalized treatment in invasive urothelial carcinoma. 病例报告:促进浸润性尿路上皮癌个性化治疗的患者衍生器官组织。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1424677
Xun Liu, Xuebing Han, Shuqing Wei, Changwen Zhang

Tumor organoids, an in-vitro three-dimensional model, possess high potential for investigating tumor biology and treatment response and have been demonstrated more appropriate for drug assessment than two-dimensional cultures. Herein, we described two cases of invasive high-grade urothelial carcinoma who underwent radical cystectomy successfully following use of patient-derived organoids (PDOs) for drug screening to inform therapeutic decisions. In these two cases, the PDOs cultured by biopsy tissues were both sensitive to the combination of gemcitabine and cisplatin. After neoadjuvant chemotherapy (NAC) with gemcitabine and cisplatin, the patients responded well, and radical cystectomy was performed successfully. No recurrence or metastasis was observed within 6 months after surgery. This small case series suggests that the patient-derived urothelial carcinoma organoids contribute to optimizing NAC options to guide personalized treatment and improve the survival outcomes.

肿瘤器官组织是一种体外三维模型,具有研究肿瘤生物学和治疗反应的巨大潜力,而且已被证明比二维培养更适合药物评估。在本文中,我们描述了两例浸润性高级别尿路上皮癌病例,这两例患者在使用患者衍生的组织器官(PDOs)进行药物筛选后成功接受了根治性膀胱切除术,为治疗决策提供了依据。在这两个病例中,活检组织培养出的PDOs均对吉西他滨和顺铂联合用药敏感。在使用吉西他滨和顺铂进行新辅助化疗(NAC)后,患者反应良好,并成功实施了根治性膀胱切除术。术后 6 个月内未发现复发或转移。这一小型病例系列表明,源自患者的尿路上皮癌器官组织有助于优化新农合方案,从而指导个性化治疗并改善生存结果。
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引用次数: 0
Development of a prognostic model incorporating a cuproptosis-related signature and CNN3 as a predictor in childhood acute myelocytic leukemia. 结合杯突相关特征和 CNN3 作为儿童急性髓细胞白血病的预测因子,建立预后模型。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1494777
Jiafan Cao, Mengyun Xie, Kexin Sun, Yijun Zhao, Jiayin Zheng, Ying Wang, Yucan Zheng, Sixi Liu, Uet Yu

Background: Childhood acute myeloid leukemia (cAML) is the second most common pediatric blood cancer, with high heterogeneity and poor prognosis. Recent studies have highlighted cuproptosis, a newly discovered form of programmed cell death triggered by the accumulation of intracellular copper ions, as a critical mechanism influencing cancer survival and resistance. Given its emerging role in cancer biology, we investigated cuproptosis-related genes (CRGs) in cAML to explore their potential in prognostic prediction and therapeutic targeting.

Methods: Gene expression data from publicly available sources were analyzed to identify differentially expressed CRGs. Samples were categorized based on their expression profiles, followed by the development of a prognostic risk model using multivariable Cox regression, LASSO, and univariable analyses. The model's performance was evaluated through Kaplan-Meier survival analysis and ROC analysis. Immune infiltration in the tumor microenvironment was assessed using ssGSEA, validated by CIBERSORT. Drug sensitivity correlations were analyzed, and functional validation experiments were conducted on THP-1 and MOLM13 cell lines to assess the role of CNN3.

Results: A set of 12 differential CRGs was used to build a robust prognostic risk model, with high accuracy in predicting patient outcomes (P < 0.001). Significant differences in immune cell composition were identified between risk groups, particularly in T cells, B cells, monocytes, and dendritic cells. Drug sensitivity analysis revealed altered IC50 values for drugs like 5-fluorouracil and bortezomib. Knockdown of CNN3 in leukemia cell lines led to reduced cell proliferation.

Conclusion: Our CRGs-based prognostic model shows potential for guiding personalized treatment strategies in cAML. The differences in immune cell infiltration between risk groups suggest that immune modulation is key in cAML progression. CNN3 and LGR4 were identified as modulators of cAML progression, making them potential therapeutic targets. Future studies with larger cohorts are essential to validate these findings and further explore CRGs-targeted therapies.

背景:儿童急性髓性白血病(cAML)是第二大最常见的儿童血癌,具有高度异质性和不良预后。最近的研究强调了杯突症--一种新发现的由细胞内铜离子积累引发的细胞程序性死亡形式--是影响癌症生存和抗药性的关键机制。鉴于其在癌症生物学中的新兴作用,我们研究了cAML中的杯突相关基因(CRGs),以探索其在预后预测和靶向治疗中的潜力:方法:分析公开来源的基因表达数据,以确定差异表达的 CRGs。根据表达谱对样本进行分类,然后利用多变量考克斯回归、LASSO和单变量分析建立预后风险模型。通过 Kaplan-Meier 生存分析和 ROC 分析评估了模型的性能。使用ssGSEA评估肿瘤微环境中的免疫浸润,并通过CIBERSORT进行验证。分析了药物敏感性相关性,并在 THP-1 和 MOLM13 细胞系上进行了功能验证实验,以评估 CNN3 的作用:结果:利用一组 12 个差异 CRGs 建立了一个稳健的预后风险模型,该模型在预测患者预后方面具有很高的准确性(P < 0.001)。不同风险组之间的免疫细胞组成存在显著差异,尤其是T细胞、B细胞、单核细胞和树突状细胞。药物敏感性分析显示,5-氟尿嘧啶和硼替佐米等药物的IC50值发生了变化。在白血病细胞系中敲除 CNN3 可减少细胞增殖:我们基于CRGs的预后模型显示出指导cAML个性化治疗策略的潜力。不同风险组间免疫细胞浸润的差异表明,免疫调节是 cAML 进展的关键。CNN3和LGR4被确定为cAML进展的调节因子,使它们成为潜在的治疗靶点。为了验证这些发现并进一步探索以CRGs为靶点的疗法,今后必须进行更大规模的研究。
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引用次数: 0
Prevalence of cancer-related fatigue, associated factors and adult cancer patients' experiences at Hawassa University Comprehensive Specialized Hospital in Ethiopia: a mixed methods study. 埃塞俄比亚哈瓦萨大学综合专科医院癌症相关疲劳的普遍性、相关因素和成年癌症患者的经历:一项混合方法研究。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fonc.2024.1480246
Tseganesh Asefa, Gedamnesh Bitew, Hiwot Tezera, Winta Tesfaye

Purpose: Cancer-related fatigue is a prevalent issue affecting 50-90% of cancer patients who experience fatigue at diagnosis, during therapy, and often for months or years after the completion of therapy. This study aimed to explore the prevalence of cancer-related fatigue, associated factors, and adult cancer patients' experiences at Hawassa University Comprehensive Specialized Hospital in Ethiopia.

Methods: A mixed-method study was conducted from February 25 to May 15, 2023, via cross-sectional descriptive and phenomenological approaches. The validated Amharic Brief Fatigue Inventory scale and semistructured interview guide were used. The data were processed via Epi-data version 4.4.3.1 and SPSS version 24, with logistic regression analysis. The interview records and field notes were transcribed and translated from Amharic to English and then analysed thematically.

Results: All participants (100%) completed the study, with 77.4% reporting significant fatigue. Fatigue was strongly associated with uninsured medical expenses (P = 0.008, OR = 3.22), late-stage cancer (P = 0.000, OR = 6.11), anaemia (P = 0.009, OR = 3.71), and comorbidities (P = 0.000, OR = 7.22). From the in-depth interviews with 16 participants, two main themes emerged: financial strain (giving up basics, and inability to work) and disease progression (intensified symptoms, increased treatment side effects, and managing multiple conditions).

Conclusion: This study revealed that 77.4% of cancer patients experience significant fatigue, which is linked to a lack of medical insurance, late-stage cancer, anaemia, and comorbid conditions. Financial strain limits access to care, whereas disease progression and managing multiple conditions intensify fatigue. Early intervention, financial support, and integrated care are crucial for reducing fatigue and improving quality of life. Future research should focus on multicentre and longitudinal studies to improve generalizability and track fatigue progression over time.

目的:癌症相关疲劳是一个普遍存在的问题,影响着 50-90% 的癌症患者,他们在确诊时、治疗期间以及治疗结束后的数月或数年内都会感到疲劳。本研究旨在探讨埃塞俄比亚哈瓦萨大学综合专科医院癌症相关疲劳的患病率、相关因素以及成年癌症患者的经历:于 2023 年 2 月 25 日至 5 月 15 日通过横断面描述法和现象学方法开展了一项混合方法研究。研究使用了经过验证的阿姆哈拉语简易疲劳量表和半结构化访谈指南。数据通过 Epi-data 4.4.3.1 版和 SPSS 24 版进行处理,并进行了逻辑回归分析。访谈记录和现场笔记均已誊写并从阿姆哈拉语翻译成英语,然后进行了专题分析:所有参与者(100%)都完成了研究,其中 77.4% 的人表示有明显的疲劳感。疲劳与未保险医疗费用(P = 0.008,OR = 3.22)、晚期癌症(P = 0.000,OR = 6.11)、贫血(P = 0.009,OR = 3.71)和合并症(P = 0.000,OR = 7.22)密切相关。在对 16 名参与者的深入访谈中,出现了两个主要的主题:经济压力(放弃基本生活、无法工作)和疾病进展(症状加剧、治疗副作用增加、管理多种疾病):这项研究表明,77.4% 的癌症患者会感到严重疲劳,这与缺乏医疗保险、癌症晚期、贫血和合并症有关。经济压力限制了患者获得医疗服务的机会,而疾病进展和多种疾病的管理则加剧了患者的疲劳感。早期干预、经济支持和综合护理对于减轻疲劳和提高生活质量至关重要。未来的研究应侧重于多中心和纵向研究,以提高普遍性并跟踪疲劳随时间的进展。
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Frontiers in Oncology
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