Construction and Analysis of an Immune-Related Gene Prognostic Index for Bladder Cancer
Construction and Analysis of an Immune-Related Gene Prognostic Index for Bladder Cancer作者机构：The First Affiliated Hospital of Yangtze University Jingzhou China
出 版 物：《Journal of Biosciences and Medicines》 (生物科学与医学（英文）)
年 卷 期：2022年第10卷第8期
页 面：82-99页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Bladder Cancer Immune-Related Genes IRGPI Survival Prognosis
摘 要：Objective: To construct an Immune-Related Gene Prognostic Index (IRGPI) for bladder cancer using a bioanalytical approach to analyze its molecular and immunological characteristics, as well as to assess the benefit of Immune Checkpoint Inhibitor (ICI) therapy in the IRGPI-defined bladder cancer subgroup. Methods: Twenty-nine immune-related pivotal genes were identified by Weighted Gene Co-expression Network Analysis (WGCNA) based on The Cancer Genome Atlas (TCGA) bladder cancer immune dataset (n = 433). Six genes were identified using a multifactorial Cox regression approach to construct the IRGPI and validated against the Gene Expression Omnibus (GEO) dataset (n = 256). Then, molecular and immunological features in the subgroups defined by IRGPI were synthesized by GSEA, Kaplan-Meier survival curves, and other methods, and the benefit of ICI treatment was assessed. Results: IRGPI was constructed based on six genes including AHNAK, ILK, OGN, PDGFD, PPARGC1B, and JAM3. Patients with low IRGPI had better Overall Survival (OS) than those with high IRGPI, which was confirmed in the validation cohort of GEO. Pooled analysis showed that the low IRGPI subgroup was associated with higher infiltration of CD8 T cells, activated memory CD4 T cells, and could benefit from ICI treatment. Meanwhile, high IRGPI subgroups were associated with higher resting memory CD4T cells, M0 macrophages, and M2 macrophage content, immunosuppression, and benefited less from ICI treatment. Conclusion: IRGPI is a novel biomarker with better efficacy in differentiating the prognosis of bladder cancer, molecular and immune features, and evaluation of ICI therapy for individualized treatment of bladder cancer.
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