Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2022 Feb 24;13:839362. doi: 10.3389/fimmu.2022.839362. eCollection 2022.
We aimed to construct and validate an energy metabolism-related gene prognostic index (EMRGPI) to predict biochemical recurrence (BCR) in patients undergoing radical prostatectomy.
We used Lasso and COX regression analysis to orchestrate the EMRGPI in the TCGA database, and the prognostic value of EMRGPI was further validated externally using the GSE46602. All analyses were conducted with R version 3.6.3 and its suitable packages.
SDC1 and ADH1B were finally used to construct the risk formula. We classified the 430 tumor patients in the TCGA database into two groups, and patients in the high-risk group had a higher risk of BCR than those in the low-risk group (HR: 1.98, 95%CI: 1.18-3.32, p=0.01). Moreover, in the GSE46602, we confirmed that the BCR risk in the high-risk group was 3.86 times higher than that in the low-risk group (95%CI: 1.61-9.24, p=0.001). We found that patients in the high-risk group had significantly higher proportions of residual tumor, older age, and T stage. SDC1 and ADH1B were significantly expressed low in the normal tissues when compared to the tumor tissues, which were opposite at the protein level. The spearman analysis showed that EMRGPI was significantly associated with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score. In addition, the EMRGPI was positively associated with the 54 immune checkpoints, among which CD80, ADORA2A, CD160, and TNFRSF25 were significantly related to the BCR-free survival of PCa patients undergoing RP.
The EMRGPI established in this study might serve as an independent risk factor for PCa patients undergoing radical prostatectomy.
本研究旨在构建并验证一个与能量代谢相关的基因预后指数(EMRGPI),以预测接受根治性前列腺切除术的患者的生化复发(BCR)。
我们使用 Lasso 和 COX 回归分析在 TCGA 数据库中构建 EMRGPI,并使用 GSE46602 外部验证 EMRGPI 的预后价值。所有分析均使用 R 版本 3.6.3 及其合适的软件包进行。
最终使用 SDC1 和 ADH1B 构建风险公式。我们将 TCGA 数据库中的 430 名肿瘤患者分为两组,高风险组的 BCR 风险高于低风险组(HR:1.98,95%CI:1.18-3.32,p=0.01)。此外,在 GSE46602 中,我们证实高风险组的 BCR 风险是低风险组的 3.86 倍(95%CI:1.61-9.24,p=0.001)。我们发现高风险组患者的肿瘤残留比例、年龄和 T 分期明显较高。与肿瘤组织相比,SDC1 和 ADH1B 在正常组织中的表达明显较低,而在蛋白水平上则相反。Spearman 分析表明,EMRGPI 与 B 细胞、CD4+T 细胞、CD8+T 细胞、中性粒细胞、巨噬细胞、树突状细胞、基质评分、免疫评分和估计评分显著相关。此外,EMRGPI 与 54 个免疫检查点呈正相关,其中 CD80、ADORA2A、CD160 和 TNFRSF25 与接受 RP 的 PCa 患者的 BCR 无复发生存显著相关。
本研究建立的 EMRGPI 可能成为接受根治性前列腺切除术的 PCa 患者的独立危险因素。