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胃癌、肠型和弥漫型以及非萎缩性胃炎活检分析:墨西哥患者杂合性缺失概述

Analysis of biopsies of gastric cancer, intestinal and diffuse, and non-atrophic gastritis: an overview of loss of heterozygosity in Mexican patients.

作者信息

Larios-Serrato Violeta, Valdez-Salazar Hilda A, Torres Javier, Camorlinga Margarita, Piña-Sánchez Patricia, Minauro Fernando, Ruiz-Tachiquín Martha-Eugenia

机构信息

Laboratorio de Biotecnología y Bioinformática Genómica/Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico.

Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias/Unidad Médica de Alta Especialidad-Hospital de Pediatría 'Dr. Silvestre Frenk Freund'/Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.

出版信息

PeerJ. 2025 Feb 25;13:e18928. doi: 10.7717/peerj.18928. eCollection 2025.

Abstract

This study analyzed the loss of heterozygosity (LOH) effect on gastric cancer (GC) tumor samples from 21 Mexican patients, including diffuse (DGC) and intestinal (IGC) subtypes, as well as non-atrophic gastritis (NAG, control). Whole-genome high-density arrays were performed, and LOH regions were identified among the tissue samples. The differences in affected chromosomes were established among groups, with chromosomes 6 and 8 primarily affected in DGC and chromosomes 3, 16, and 17 in IGC. Functional pathway analysis revealed involvement in cancer-associated processes, such as signal transduction, immune response, and cellular metabolism. Five LOH-genes (IRAK1, IKBKG, PAK3, TKTL1, PRPS1) shared between GC and NAG suggest an early role in carcinogenesis. Specific genes were highlighted for Hallmarks of Cancer NAG-related genes (PTPRJ and NDUFS) were linked to cell proliferation and growth; IGC genes (GNAI2, RHOA, MAPKAPK3, MST1R) to genomic instability, metastasis, and arrest of cell death; and DGC genes to energy metabolism and immune evasion. These findings emphasize the role of LOH in GC pathogenesis and underscore the need for further research to understand LOH-affected genes and their diagnostic or evolution potential in cancer management. Portions of this text were previously published as part of a preprint (https://www.medrxiv.org/content/10.1101/2024.07.29.24311063v1).

摘要

本研究分析了杂合性缺失(LOH)对21名墨西哥患者胃癌(GC)肿瘤样本的影响,这些样本包括弥漫型(DGC)和肠型(IGC)亚型,以及非萎缩性胃炎(NAG,对照)。进行了全基因组高密度阵列分析,并在组织样本中鉴定出LOH区域。确定了各组之间受影响染色体的差异,DGC中主要受影响的染色体是6号和8号,IGC中是3号、16号和17号染色体。功能通路分析显示其参与了癌症相关过程,如信号转导、免疫反应和细胞代谢。GC和NAG之间共有的五个LOH基因(IRAK1、IKBKG、PAK3、TKTL1、PRPS1)表明其在致癌作用中起早期作用。突出了与癌症特征相关的特定基因,NAG相关基因(PTPRJ和NDUFS)与细胞增殖和生长有关;IGC基因(GNAI2、RHOA、MAPKAPK3、MST1R)与基因组不稳定、转移和细胞死亡停滞有关;DGC基因与能量代谢和免疫逃逸有关。这些发现强调了LOH在GC发病机制中的作用,并强调需要进一步研究以了解受LOH影响的基因及其在癌症管理中的诊断或进化潜力。本文的部分内容曾作为预印本的一部分发表(https://www.medrxiv.org/content/10.1101/2024.07.29.24311063v1)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8957/11869887/d84879a23cfc/peerj-13-18928-g001.jpg

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