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整合生物信息学分析鉴定 COL11A1 为胰腺腺癌中与免疫浸润相关的预后标志物。

Integrated bioinformatics analysis identified COL11A1 as an immune infiltrates correlated prognosticator in pancreatic adenocarcinoma.

机构信息

Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Acornmed Biotechnology Co., Ltd., Beijing, China.

出版信息

Int Immunopharmacol. 2021 Jan;90:106982. doi: 10.1016/j.intimp.2020.106982. Epub 2020 Oct 29.

Abstract

Pancreatic adenocarcinoma (PAAD) is the most common pancreatic cancer, with high mortality rate and limited treatment options. Tumor infiltrating cells and genes in microenvironment are emerging as pivotal players in PAAD progression and prognosis. In this study, we obtained genes expression data set GSE119794 of PAAD, which contains data from 10 tumor and 10 normal samples. A total of 262 differentially expressed genes (DEGs), including 169 up-regulated and 93 down-regulated genes, were obtained based on expression fold change and significance. Combining the pathway analysis of DEGs and GSEA analysis of all genes, four KEGG pathways were enriched. The 4 pathways include pancreatic secretion, protein digestion and absorption, fat digestion and absorption, and PPAR signaling pathways. Functional enrichment of Gene Ontology significantly enriched extracellular matrix, an important component in microenvironment. In the Protein-protein interaction (PPI) network, we screened out 3 hub genes of COL11A1, KRT19 and CXCL5 by CytoHubba. At last, the expression level, prognostic significance and correlation with tumor infiltrates were validated in TCGA database, with GEPIA and TIMER. The validation identified Collagen Type XI Alpha 1 Chain (COL11A1), an extracellular matrix structural constituent, as a hazardous prognosticator with significant correlation with macrophage, neutrophil and dendritic cells. In sum, we identified COL11A1 as an immune infiltrates correlated prognosticator in pancreatic adenocarcinoma.

摘要

胰腺导管腺癌(PAAD)是最常见的胰腺癌,死亡率高,治疗选择有限。肿瘤浸润细胞和微环境中的基因正在成为 PAAD 进展和预后的关键因素。在这项研究中,我们获得了 PAAD 的基因表达数据集 GSE119794,其中包含 10 个肿瘤和 10 个正常样本的数据。基于表达倍数变化和显著性,共获得 262 个差异表达基因(DEGs),包括 169 个上调基因和 93 个下调基因。结合 DEGs 的通路分析和所有基因的 GSEA 分析,有 4 个 KEGG 通路富集。这 4 条通路包括胰腺分泌、蛋白质消化吸收、脂肪消化吸收和 PPAR 信号通路。基因本体论的功能富集显著富集了细胞外基质,这是微环境中的一个重要组成部分。在蛋白质-蛋白质相互作用(PPI)网络中,我们通过 CytoHubba 筛选出 COL11A1、KRT19 和 CXCL5 这 3 个 hub 基因。最后,在 TCGA 数据库中,通过 GEPIA 和 TIMER 验证了它们的表达水平、预后意义和与肿瘤浸润的相关性。验证结果确定了胶原类型 XI Alpha 1 链(COL11A1)作为一个危险的预后预测因子,与巨噬细胞、中性粒细胞和树突状细胞有显著相关性。总之,我们确定 COL11A1 是胰腺导管腺癌中与免疫浸润相关的预后预测因子。

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