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鉴定膀胱癌的免疫相关基因作为预后因素。

Identification of immune-related genes as prognostic factors in bladder cancer.

机构信息

Department of Oncology, Changzhou Traditional Chinese Medical Hospital, Changzhou, 213003, Jiangsu, People's Republic of China.

Department of Oncology, Jining Tumour Hospital, Jining, People's Republic of China.

出版信息

Sci Rep. 2020 Nov 12;10(1):19695. doi: 10.1038/s41598-020-76688-w.

DOI:10.1038/s41598-020-76688-w
PMID:33184436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7661532/
Abstract

Bladder cancer is one of the most common cancers worldwide. The immune response and immune cell infiltration play crucial roles in tumour progression. Immunotherapy has delivered breakthrough achievements in the past decade in bladder cancer. Differentially expressed genes and immune-related genes (DEIRGs) were identified by using the edgeR package. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment analysis of DEIRGs. Survival-associated IRGs were identified by univariate Cox regression analysis. A prognostic model was established by univariate COX regression analysis, and verified by a validation prognostic model based on the GEO database. Patients were divided into high-risk and low-risk groups based on the median risk score value for immune cell infiltration and clinicopathological analyses. A regulatory network of survival-associated IRGs and potential transcription factors was constructed to investigate the potential regulatory mechanisms of survival-associated IRGs. Nomogram and ROC curve to verify the accuracy of the model. Quantitative real-time PCR was performed to validate the expression of relevant key genes in the prognostic model. A total of 259 differentially expressed IRGs were identified in the present study. KEGG pathway analysis of IRGs showed that the "cytokine-cytokine receptor interaction" pathway was the most significantly enriched pathway. Thirteen survival-associated IRGs were selected to establish a prognostic index for bladder cancer. In both TCGA prognostic model and GEO validation model, patients with high riskscore had worse prognosis compared to low riskscore group. A high infiltration level of macrophages was observed in high-risk patients. OGN, ELN, ANXA6, ILK and TGFB3 were identified as hub survival-associated IRGs in the network. EBF1, WWTR1, GATA6, MYH11, and MEF2C were involved in the transcriptional regulation of these survival-associated hub IRGs. The present study identified several survival-associated IRGs of clinical significance and established a prognostic index for bladder cancer outcome evaluation for the first time.

摘要

膀胱癌是全球最常见的癌症之一。免疫反应和免疫细胞浸润在肿瘤进展中起着至关重要的作用。免疫疗法在过去十年中在膀胱癌治疗中取得了突破性的成就。使用 edgeR 包鉴定差异表达基因和免疫相关基因 (DEIRGs)。对 DEIRGs 进行基因本体论注释和京都基因与基因组百科全书 (KEGG) 通路分析，以进行功能富集分析。通过单因素 Cox 回归分析鉴定与生存相关的 IRGs。通过单因素 COX 回归分析建立预后模型，并通过基于 GEO 数据库的验证预后模型进行验证。根据免疫细胞浸润和临床病理分析的中位风险评分值，将患者分为高风险和低风险组。构建生存相关 IRGs 和潜在转录因子的调控网络，以研究生存相关 IRGs 的潜在调控机制。列线图和 ROC 曲线验证模型的准确性。进行定量实时 PCR 以验证预后模型中相关关键基因的表达。本研究共鉴定出 259 个差异表达的 IRGs。IRGs 的 KEGG 通路分析表明，“细胞因子-细胞因子受体相互作用”途径是最显著富集的途径。选择 13 个与生存相关的 IRGs 建立膀胱癌预后指数。在 TCGA 预后模型和 GEO 验证模型中，高风险评分患者的预后均较低风险评分患者差。高风险患者中观察到巨噬细胞浸润水平较高。OGN、ELN、ANXA6、ILK 和 TGFB3 被鉴定为网络中与生存相关的关键 IRGs。EBF1、WWTR1、GATA6、MYH11 和 MEF2C 参与了这些与生存相关的关键 IRGs 的转录调控。本研究首次鉴定了一些具有临床意义的与生存相关的 IRGs，并建立了膀胱癌预后评估的预后指数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/c31ed32a772e/41598_2020_76688_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/7f7eb145cafd/41598_2020_76688_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/cc174e0ae91a/41598_2020_76688_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/fca56c149590/41598_2020_76688_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/cd92d9467704/41598_2020_76688_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/084ad9991e82/41598_2020_76688_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/d770c3869c77/41598_2020_76688_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/b13b3e039efe/41598_2020_76688_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/c31ed32a772e/41598_2020_76688_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/7f7eb145cafd/41598_2020_76688_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/cc174e0ae91a/41598_2020_76688_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/fca56c149590/41598_2020_76688_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/cd92d9467704/41598_2020_76688_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/084ad9991e82/41598_2020_76688_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/d770c3869c77/41598_2020_76688_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/b13b3e039efe/41598_2020_76688_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7a8/7661532/c31ed32a772e/41598_2020_76688_Fig8_HTML.jpg

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本文引用的文献

[1]
Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

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Immune signature profiling identified prognostic factors for gastric cancer.

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