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生物信息学分析鉴定出与弥漫型胃癌预后不良相关的生物标志物。

Bioinformatics analysis identifies biomarkers associated with poor prognosis in diffuse‑type gastric cancer.

机构信息

Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.

出版信息

Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11832. Epub 2021 Jan 26.

DOI:10.3892/mmr.2021.11832
PMID:33495829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7809905/
Abstract

Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffuse‑type GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the 'limma' and 'survival' R packages. A total of 355 survival‑related DEGs were selected according to specific screening criteria, of which 293 were associated with diffuse‑type GC and 62 with intestinal‑type GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional annotation and pathway enrichment analysis of DEGs. Using protein‑protein interaction networks and Cytoscape software, three hub genes were identified in diffuse‑type GC‑associated DEGs, including angiotensinogen (AGT), C‑X‑C motif chemokine ligand 12 (CXCL12) and adrenoceptor β2 (ADRB2). Immunohistochemical staining and reverse transcription‑quantitative PCR revealed that the expression levels of the three genes in diffuse‑type GC samples were upregulated compared with in intestinal‑type GC samples. Kaplan Meier analysis indicated that a higher expression levels of these three hub genes were associated with a poorer prognosis of diffuse‑type GC. In summary, the present findings suggested that AGT, CXCL12 and ADRB2 might contribute to the progression of diffuse‑type GC, and could serve as potential biomarkers or therapeutic targets for this disease.

摘要

胃癌(GC)是消化系统最常见的恶性肿瘤之一。弥漫型 GC 分化程度相对较差,远处转移和淋巴结转移的概率较高,临床预后较差。本研究旨在寻找能预测不同类型 GC 预后的特异基因。采用‘limma’和‘survival’R 包对从基因表达综合数据库获取的 GSE62254 数据集进行差异表达基因(DEGs)筛选。根据特定的筛选标准共选择了 355 个与生存相关的 DEGs,其中 293 个与弥漫型 GC 相关,62 个与肠型 GC 相关。采用基因本体论和京都基因与基因组百科全书对 DEGs 进行功能注释和通路富集分析。利用蛋白-蛋白相互作用网络和 Cytoscape 软件,在弥漫型 GC 相关 DEGs 中鉴定到三个枢纽基因,包括血管紧张素原(AGT)、C-X-C 基序趋化因子配体 12(CXCL12)和肾上腺素能受体β2(ADRB2)。免疫组织化学染色和反转录定量 PCR 显示,这三个基因在弥漫型 GC 样本中的表达水平高于肠型 GC 样本。Kaplan-Meier 分析表明,这三个枢纽基因的高表达水平与弥漫型 GC 的预后不良相关。综上所述,本研究结果表明,AGT、CXCL12 和 ADRB2 可能促进弥漫型 GC 的进展,可能作为该疾病潜在的生物标志物或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f2f/7809905/edfa762ec52a/mmr-23-03-11832-g06.jpg
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本文引用的文献

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Front Oncol. 2020 Aug 3;10:1212. doi: 10.3389/fonc.2020.01212. eCollection 2020.
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ICAM1 Regulates the Development of Gastric Cancer and May Be a Potential Biomarker for the Early Diagnosis and Prognosis of Gastric Cancer.细胞间黏附分子1调控胃癌的发展,可能是胃癌早期诊断和预后的潜在生物标志物。
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