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识别和验证肾透明细胞癌肿瘤免疫微环境相关预后基因。

Identification and Verification of Tumor Immune Microenvironment-Related Prognostic Genes in Kidney Renal Clear Cell Carcinoma.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Cardiovascular Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Biomed Res Int. 2022 Jan 27;2022:5563668. doi: 10.1155/2022/5563668. eCollection 2022.

Abstract

BACKGROUND

The tumor immune microenvironment is vital to kidney renal clear cell carcinoma (KIRC) progression, and immunotherapies have been shown to be effective in the management of KIRC. However, the prognostic genes associated with the tumor immune microenvironment in KIRC have not been fully identified. We obtained the KIRC RNA sequencing data and the clinical characteristics from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. We screened the gene modules associated with the tumor immune microenvironment based on the ESTIMATE algorithm and weighted gene coexpression network analysis (WGCNA). Univariate Cox analysis and the LASSO method were used to construct a prognostic model. Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the accuracy of our risk model. TIMER and Single-Sample Gene Set Enrichment Analysis (ssGSEA) were used to explore the correlation between prognostic genes and immune cell infiltration.

RESULTS

Fifty-four genes in modules were significantly associated with the overall survival (OS) time of patients with KIRC. Furthermore, 12 hub genes were selected to construct the prognostic model. The prognostic model showed superior accuracy in both TCGA and ICGC cohorts using ROC curve analysis. Systematic analysis of immune cell infiltration revealed that nine genes were significantly correlated with levels of tumor-infiltrating immune cells.

CONCLUSIONS

Our findings indicated that the tumor immune microenvironment was an important determinant of KIRC outcomes and revealed potential biomarkers for predicting patient OS and for targeted immunotherapies.

摘要

背景

肿瘤免疫微环境对肾透明细胞癌(KIRC)的进展至关重要,免疫疗法已被证明在 KIRC 的治疗中有效。然而,与 KIRC 肿瘤免疫微环境相关的预后基因尚未完全确定。我们从癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)数据库中获得了 KIRC 的 RNA 测序数据和临床特征。我们基于 ESTIMATE 算法和加权基因共表达网络分析(WGCNA)筛选了与肿瘤免疫微环境相关的基因模块。单因素 Cox 分析和 LASSO 方法用于构建预后模型。接受者操作特征(ROC)曲线分析用于评估我们风险模型的准确性。TIMER 和单样本基因集富集分析(ssGSEA)用于探讨预后基因与免疫细胞浸润之间的相关性。

结果

模块中 54 个基因与 KIRC 患者的总生存期(OS)时间显著相关。此外,选择了 12 个枢纽基因来构建预后模型。ROC 曲线分析表明,该预后模型在 TCGA 和 ICGC 队列中的准确性均较高。免疫细胞浸润的系统分析表明,有 9 个基因与肿瘤浸润免疫细胞的水平显著相关。

结论

我们的研究结果表明,肿瘤免疫微环境是 KIRC 结果的重要决定因素,并揭示了预测患者 OS 和靶向免疫治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6934/8813216/635c3808f01a/BMRI2022-5563668.001.jpg

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