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胰头癌与胰体尾癌的比较生物信息学分析。

Comparative bioinformatical analysis of pancreatic head cancer and pancreatic body/tail cancer.

机构信息

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Pancreas Institute of Nanjing Medical University, Nanjing, 210029, People's Republic of China.

出版信息

Med Oncol. 2020 Apr 10;37(5):46. doi: 10.1007/s12032-020-01370-0.

Abstract

This study is to analyze differentially expressed genes (DEGs) and mutation signatures of pancreatic head cancer and pancreatic body/tail cancer. Pancreatic Adenocarcinoma (PAAD) RNA-seq data, mutation data and clinical data were downloaded and collected from The Cancer Genome Atlas (TCGA), FireHose and CBioPortal. According to the anatomic location, the patients were divided into 146 cases of pancreatic head cancer and 28 cases of pancreatic body/tail cancer. Then survival analysis was performed by Kaplan-Meier and log-rank test. Furthermore, DEGs were screened by R package Deseq2. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) were then carried out by DAVID and String. Online tool TIMER was used to analyze the immune cells infiltration. R package maftools and GenVisR were applied to analyze frequently mutated genes and mutant-allele tumor heterogeneity (MATH) of PAAD. Survival of patients with pancreatic body/tail cancer was better than those with pancreatic head cancer (median survival, 24.05 vs 19.45 months, p = 0.048). And 496 significant DEGs (|log2 FoldChange| > 1.5,false discovery rate (FDR) < 0.05) were identified, including 253 downregulated genes and 243 upregulated genes. And there were 13 Go terms (4 biological processes, 6 cellular components and 3 molecular functions) and 3 KEGG pathways (Pancreatic secretion, Fat digestion and absorption, Protein digestion and absorption) (FDR < 0.05). B cells and CD4 + T cells infiltration were more significant in pancreatic head cancer. MATH scores of pancreatic body/tail cancer were higher than pancreatic head cancer, while χ test of top 10 frequently mutated genes showed little difference between them. There were prognostic and genetic differences between pancreatic head cancer and pancreatic body/tail cancer. PAAD originated from different location may have different biology natures and should not be treated with same strategy.

摘要

本研究旨在分析胰腺头癌和胰腺体/尾癌的差异表达基因(DEGs)和突变特征。从癌症基因组图谱(TCGA)、FireHose 和 CBioPortal 下载并收集胰腺腺癌(PAAD)RNA-seq 数据、突变数据和临床数据。根据解剖位置,将患者分为 146 例胰腺头癌和 28 例胰腺体/尾癌。然后通过 Kaplan-Meier 和对数秩检验进行生存分析。此外,通过 R 包 Deseq2 筛选 DEGs。通过 DAVID 和 String 进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)和蛋白质-蛋白质相互作用(PPI)分析。使用在线工具 TIMER 分析免疫细胞浸润。应用 R 包 maftools 和 GenVisR 分析 PAAD 的高频突变基因和突变等位基因肿瘤异质性(MATH)。胰腺体/尾癌患者的生存情况优于胰腺头癌患者(中位生存时间,24.05 个月比 19.45 个月,p=0.048)。鉴定出 496 个显著的 DEGs(|log2 FoldChange|>1.5,错误发现率(FDR)<0.05),包括 253 个下调基因和 243 个上调基因。有 13 个 GO 术语(4 个生物过程、6 个细胞成分和 3 个分子功能)和 3 个 KEGG 通路(胰腺分泌、脂肪消化吸收、蛋白质消化吸收)(FDR<0.05)。在胰腺头癌中,B 细胞和 CD4+T 细胞浸润更为显著。胰腺体/尾癌的 MATH 评分高于胰腺头癌,而前 10 个高频突变基因的 χ 检验显示它们之间差异不大。胰腺头癌和胰腺体/尾癌之间存在预后和遗传差异。起源于不同部位的 PAAD 可能具有不同的生物学特性,不应采用相同的治疗策略。

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