一组墨西哥患者胃癌中的杂合性缺失

V. Larios-Serrato, Hilda A. Valdez-Salazar, Javier Torres, M. Camorlinga-Ponce, P. Piña-Sánchez, Fernando Minauro-Sanmiguel, M. Ruiz-Tachiquín, Dr Martha-Eugenia Ruiz-Tachiquín, Av, Cuauhtémoc, Colonia
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引用次数: 0

摘要

在全球范围内,胃癌(GC)是一种常见的恶性肿瘤,是死亡率最高的消化系统疾病。目前对胃癌和杂合性缺失(LOH)的研究与了解肿瘤生物学和确定癌症的基本方面有关。本研究纯化了弥漫性胃癌(DGC)、肠道胃癌(IGC)或非萎缩性胃炎(NAG;对照组)墨西哥患者的 DNA 样本,并进行了全基因组高密度阵列分析。随后,在组织样本中确定了 LOH,并分析了癌基因和信号通路,以确定变化最大的基因。通过详细的生物信息学分析,根据 LOH 在患者样本中的频率、参与代谢通路的情况、网络交互作用以及癌症标志基因的富集情况,将 LOH 与癌症标志联系起来。GC 中的 LOH 基因包括 PTPR、NDUFS3、PAK3、IRAK1、IKBKG、TKTL1、PRPS1、GNAI2、RHOA、MAPKA 和 MST1R。NAG 的突出基因涉及增殖和生长;IGC 的基因引发基因组不稳定性、组织侵袭、转移和细胞死亡停滞;DGC 的基因涉及能量代谢、免疫逃避的破坏和复制永生。其他事件,如持续的血管生成,在 NAG-IGC-DGC 之间也很相似。总之,这些都是必须对 GC 患者进行监测的分子、细胞和代谢事件。我们的研究结果必须经过验证,才能开发出用于诊断、预后、治疗反应的分子检测方法,最重要的是,还能开发出筛查检测方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Loss of heterozygosity in gastric cancers in a set of Mexican patients
Worldwide, gastric cancer (GC) is a common malignancy with the highest mortality rate among digestive system diseases. The present study of GC and loss of heterozygosity (LOH) is relevant to understanding tumor biology and establishing essential aspects of cancer. Here, DNA samples from Mexican patients with diffuse GC (DGC), intestinal GC (IGC), or non-atrophic gastritis (NAG; control) were purified, and whole-genome high-density arrays were performed. Posteriorly, LOH was identified among the tissue samples, and cancer genes and signaling pathways were analyzed to determine the most altered. Detailed bioinformatics analysis was developed to associate LOH with the Hallmarks of Cancer according to their frequency in patient samples, participation in metabolic pathways, network interactions, and enrichment of Cancer Hallmark genes. LOH-genes in GC were PTPR, NDUFS3, PAK3, IRAK1, IKBKG, TKTL1, PRPS1, GNAI2, RHOA, MAPKA, and MST1R. Genes that stand out at NAG involve proliferation and growth; those at IGC trigger genomic instability, tissue invasion, metastasis, and arrest of cell death; and those at DGC involve energy metabolism, the destruction of immune evasion, and replicative immortality. Other events, such as sustained angiogenesis, were similar between NAG-IGC-DGC. Together, these are molecular, cellular, and metabolic events that must be monitored in GC patients. Our findings must be validated to develop molecular tests for diagnosis, prognosis, treatment response, and, most importantly, screening tests.
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