Luan Jiao-Chen, Zhang Qi-Jie, Zhao Kai, Zhou Xiang, Yao Liang-Yu, Zhang Tong-Tong, Zeng Teng-Yue, Xia Jia-Dong, Song Ning-Hong
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
The Affiliated Kezhou People's Hospital of Nanjing Medical University, Kezhou, Xinjiang, China.
J Cancer. 2021 May 1;12(12):3715-3725. doi: 10.7150/jca.51059. eCollection 2021.
Decision-making regarding biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) mainly relies on clinicopathological parameters with a low predictive accuracy. Currently, accumulating evidence suggests that immune-associated genes (IAGs) play irreplaceable roles in tumorigenesis, progression and metastasis. Considering the critical role of immune in PCa, we therefore attempted to identify the novel IAGs signature and validate its prognostic value that can better forecast the risk for BCR and guide clinical treatment. RNA-sequencing and corresponding clinicopathological data were downloaded from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was utilized to screen out the candidate module closely related to BCR, and univariate and LASSO Cox regression analyses were performed to build the gene signature. Kaplan-Meier (KM) survival analysis, time-dependent receiver operating curve (ROC), independent prognostic analysis and nomogram were also applied to evaluate the prognostic value of the signature. Besides, Gene ontology analysis (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to explore potential biological pathways. A total of six IAGs (SSTR1, NFATC3, NRP1, TUBB3, IL1R1, GDF15) were eventually identified and used to establish a novel IAGs signature. The Kaplan-Meier analysis revealed that patients with low-risk scores had longer recurrence-free survival (RFS) than those with high-risk scores in both GSE70769 and TCGA cohorts. Further, our signature was also proven to be a valuable independent prognostic factor for BCR. We also constructed a nomogram based on the gene signature and related clinicopathologic features, which excellently predict 1-year, 3-year and 5-year prognosis of localized PCa patients after RP. Moreover, functional enrichment analysis demonstrated the vital biological processes, and stratified GSEA revealed that a crucial immune-related pathway (T cell receptor signaling pathway) was notably enriched in the high-risk group. We successfully developed a novel robust IAGs signature that is powerful in BCR prediction in localized PCa patients after RP, and created a prognostic nomogram. In addition, the signature might help clinicians in selecting high-risk subpopulation, predicting survival status of patients and promoting more individualized therapies than traditional clinical factors.
根治性前列腺切除术后局限性前列腺癌（PCa）患者生化复发（BCR）的决策主要依赖于临床病理参数，但其预测准确性较低。目前，越来越多的证据表明，免疫相关基因（IAGs）在肿瘤发生、发展和转移中发挥着不可替代的作用。鉴于免疫在PCa中的关键作用，我们试图确定新的IAGs特征并验证其预后价值，以更好地预测BCR风险并指导临床治疗。从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库下载了RNA测序数据和相应的临床病理数据。利用加权基因共表达网络分析（WGCNA）筛选出与BCR密切相关的候选模块，并进行单变量和LASSO Cox回归分析以构建基因特征。还应用Kaplan-Meier（KM）生存分析、时间依赖性受试者工作特征曲线（ROC）、独立预后分析和列线图来评估该特征的预后价值。此外，使用基因本体分析（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）来探索潜在的生物学途径。最终共鉴定出6个IAGs（SSTR1、NFATC3、NRP1、TUBB3、IL1R1、GDF15），并用于建立新的IAGs特征。Kaplan-Meier分析显示，在GSE70769和TCGA队列中，低风险评分患者的无复发生存期（RFS）均长于高风险评分患者。此外，我们的特征也被证明是BCR的一个有价值的独立预后因素。我们还基于基因特征和相关临床病理特征构建了列线图，该列线图能很好地预测根治性前列腺切除术后局限性PCa患者1年、3年和5年的预后。此外，功能富集分析揭示了重要的生物学过程，分层GSEA显示一个关键的免疫相关途径（T细胞受体信号通路）在高风险组中显著富集。我们成功开发了一种新的强大的IAGs特征，它在预测根治性前列腺切除术后局限性PCa患者的BCR方面具有强大作用，并创建了一个预后列线图。此外，该特征可能有助于临床医生选择高风险亚群、预测患者的生存状态，并促进比传统临床因素更具个性化的治疗。
