Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, China.
Aging (Albany NY). 2023 Nov 22;15(22):13213-13238. doi: 10.18632/aging.205237.
Programmed cell death (PCD), a common modality of cell death, affects tumor development and acts as a target for tumor therapeutics. Many modalities of PCD regulate genesis, progression and metastasis of cancers, thus affecting the patients' prognosis, but the comprehensive molecular mechanisms of PCD in tumors are lacking, especially in renal cancer. Here, seventeen PRPCDGs were identified from 1257 genes associated with thirteen PCD modalities, which were highly differentially expressed and significantly affected patients' prognosis. Then, LASSO regression analysis of these PRPCDGs screened the 9-gene PRPCDGs risk signature in TCGA-KIRC database. The PRPCDGs risk signature was closely associated with the patients' prognosis and presented stable prediction efficacy for 5- and 7-year overall survival (OS) in three different cohorts of renal cancer. Immune cell infiltration, immune checkpoint expression and pathway enrichment (including GO, KEGG pathway, tumor-associated pathways and metabolism-associated pathways) were significantly different in the high- or low-PRPCDGs-risk group. Finally, we illustrated that TRIB3 might be a protumor factor responsible for the elevated proliferation and invasion capacities of renal cell carcinoma (RCC) cells. In summary, the PRPCDGs risk signature was developed and showed stable prediction efficacy for the prognosis of patients and that (such as TRIB3) could be a potential target for RCC management.
程序性细胞死亡(PCD)是一种常见的细胞死亡方式,影响肿瘤的发生发展,并成为肿瘤治疗的靶点。PCD 的多种形式调节癌症的发生、进展和转移,从而影响患者的预后,但肿瘤中 PCD 的综合分子机制尚不清楚,尤其是在肾癌中。在这里,从与 13 种 PCD 形式相关的 1257 个基因中鉴定出了 17 个 PRPCDGs,这些基因高度差异表达,并显著影响患者的预后。然后,通过 TCGA-KIRC 数据库中的 LASSO 回归分析筛选出这些 PRPCDGs 的 9 个基因 PRPCDGs 风险特征。PRPCDGs 风险特征与患者的预后密切相关,并在三个不同的肾癌队列中对 5 年和 7 年的总生存(OS)具有稳定的预测效力。在高或低 PRPCDGs 风险组中,免疫细胞浸润、免疫检查点表达和途径富集(包括 GO、KEGG 途径、肿瘤相关途径和代谢相关途径)存在显著差异。最后,我们说明了 TRIB3 可能是一个促进肿瘤的因素,负责提高肾细胞癌(RCC)细胞的增殖和侵袭能力。总之,PRPCDGs 风险特征被开发出来,并对患者的预后具有稳定的预测效力,并且(如 TRIB3)可能是 RCC 管理的潜在靶点。