III 期胃癌中肿瘤突变负荷与预后的关系及其临床意义

IF 2.2 4区 工程技术 Q3 PHARMACOLOGY & PHARMACY
Bioimpacts Pub Date : 2024-03-02 DOI:10.34172/bi.2024.30118
Ya-Lin Han, Li Chen, Xu-Ning Wang, Mao-Lin Xu, Rui Qin, F. Gong, Peng Sun, Hong-yi Liu, Zhi-Peng Teng, Zhao-Xia Li, Guang-Hai Dai
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引用次数: 0

摘要

研究背景目的:探讨 III 期胃癌(GC)患者的肿瘤突变负荷(TMB)与预后的相关性及其临床意义。研究方法在38名患者组成的研究队列和173名患者组成的癌症基因组图谱(TCGA)队列中,III期胃癌患者被分为高TMB组和低TMB组。在研究队列中,使用新一代测序技术检测突变的 GC 基因并获得 TMB 数据。在TCGA队列中,进行了基因组富集分析,并分析了TMB、预后和临床病理因素之间的关系。采用 Western 印迹和定量实时聚合酶链反应检测蛋白质和基因的表达水平。使用甲基噻唑四氮唑和透孔细胞检测法测量细胞活力。结果显示在两个队列中,高TMB组患者的总生存率(OS)均优于低TMB组患者,且TMB与年龄、突变特征1和突变特征17相关。Cox 回归分析显示,年龄而非 TMB 是独立的预后因素。此外,高频突变基因明显富集于Notch和RTK-RAS信号通路。与低TMB组相比,高TMB组这些通路的激活程度较低,而两组GC细胞的增殖和迁移能力显示出相似的模式。结论高TMB组患者的OS率高于低TMB组患者。高频突变基因明显富集于 RTK-RAS 和 Notch 通路。因此,TMB可作为一种预后生物标志物,具有潜在的临床意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer
Background: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the Notch and RTK-RAS signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.
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来源期刊
Bioimpacts
Bioimpacts Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.80
自引率
7.70%
发文量
36
审稿时长
5 weeks
期刊介绍: BioImpacts (BI) is a peer-reviewed multidisciplinary international journal, covering original research articles, reviews, commentaries, hypotheses, methodologies, and visions/reflections dealing with all aspects of biological and biomedical researches at molecular, cellular, functional and translational dimensions.
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