Identification of effect of gene mutations related to telomere maintenance in gastric cancer patients

Anju R. Nath, Jeyakumar Natarajan
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Abstract

Background

Mutations in gastric cancer may remain harmless despite mutations that can turn oncogenic. Although omics technologies have supplied a clear view of mutations and driver genes in cancers, the pathology of gastric cancer still is unknown.

Objective

This study aims to understand mutations of genes that relate to telomere maintenance in gastric cancer.

Methods

We used transcriptomic and proteomic data from normal and gastric cancer patients to decide the relationship between genes and proteins. We ranked the gene-protein pairs with the Spearman correlation and subjected the differently ranked genes for functional analysis. We performed the co-expression analysis to select the genes from functional analysis. Then we assessed the selected genes for mutations and thereafter neoantigen analysis.

Results

We identified 20 genes through differential ranking based on Spearman correlation of gene-protein pairs. Among these, ERCC1, MRE11A, RAD50, TP53BP1, and YWHAE were linked to critical functions like DNA repair, apoptosis, and stress response. Gene prioritization focused on these five genes, and from them through gene co-expression, RAD50, TP53BP1, and YWHAE were selected. Mutational analysis revealed prevalent C > T and G > A mutations. These genes were associated with elderly patients, specific histologic grades, and types of gastric cancer. Importantly, these mutations generated neoantigens with potential for immunotherapeutic targeting.

Conclusion

Our extensive research shows the complex genetic makeup of gastric cancer and its potential effects on diagnosis and treatment. The identified genes and the mutations linked to them offer important information on the molecular processes behind gastric cancer progression. These results set the foundation for additional research and immunotherapeutic applications in the field of gastric cancer.

胃癌患者端粒维持相关基因突变影响的鉴定
胃癌的突变可能是无害的,尽管突变可以变成致癌的。虽然组学技术已经为癌症的突变和驱动基因提供了清晰的视角,但胃癌的病理仍然是未知的。本研究旨在了解胃癌中与端粒维持相关的基因突变。我们利用正常和胃癌患者的转录组学和蛋白质组学数据来确定基因和蛋白质之间的关系。我们根据Spearman相关性对基因-蛋白对进行排序,并对不同排序的基因进行功能分析。我们进行共表达分析,从功能分析中选择基因。然后我们评估所选基因的突变,然后进行新抗原分析。通过基因-蛋白对Spearman相关的差异排序,鉴定出20个基因。其中,ERCC1、MRE11A、RAD50、TP53BP1和YWHAE与DNA修复、细胞凋亡和应激反应等关键功能有关。对这5个基因进行基因优先排序,通过基因共表达,从中筛选出RAD50、TP53BP1和YWHAE。突变分析显示普遍存在C>T和G>A突变。这些基因与老年患者、特定的组织学分级和胃癌类型相关。重要的是,这些突变产生了具有免疫治疗靶向潜力的新抗原。我们广泛的研究表明胃癌的复杂基因组成及其对诊断和治疗的潜在影响。鉴定出的基因和与之相关的突变为胃癌进展背后的分子过程提供了重要信息。这些结果为胃癌领域的进一步研究和免疫治疗应用奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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