Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Graduate School, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Genes (Basel). 2022 Mar 30;13(4):620. doi: 10.3390/genes13040620.
Lactic acid was previously considered a waste product of glycolysis, and has now become a key metabolite for cancer development, maintenance and metastasis. So far, numerous studies have confirmed that tumor lactic acid levels are associated with increased metastasis, tumor recurrence and poor prognosis. However, the prognostic value of lactic acid metabolism and transporter related genes in patients with clear cell renal cell carcinoma has not been explored. We selected lactic acid metabolism and transporter related twenty-one genes for LASSO cox regression analysis in the E-MTAB-1980 cohort, and finally screened three genes (PNKD, SLC16A8, SLC5A8) to construct a clinical prognostic model for patients with clear cell renal cell carcinoma. Based on the prognostic model we constructed, the over survival (hazard ratio = 4.117, 95% CI: 1.810−9.362, p < 0.0001) of patients in the high-risk group and the low-risk group in the training set E-MTAB-1980 cohort had significant differences, and similar results (hazard ratio = 1.909, 95% CI: 1.414−2.579 p < 0.0001) were also observed in the validation set TGCA cohort. Using the CIBERSORT algorithm to analyze the differences in immune cell infiltration in different risk groups, we found that dendritic cells, M1 macrophages, and CD4+ memory cells in the high-risk group were significantly lower than those in the low-risk group, while Treg cells were higher than in the low-risk group. Finally, through gene enrichment analysis, we found that the signal pathway that is strongly related to the prognostic model is the cell cycle.
乳酸过去被认为是糖酵解的一种废物产物,现在已成为癌症发展、维持和转移的关键代谢物。到目前为止,大量研究已经证实,肿瘤乳酸水平与转移增加、肿瘤复发和预后不良有关。然而,乳酸代谢和转运相关基因在透明细胞肾细胞癌患者中的预后价值尚未得到探索。我们在 E-MTAB-1980 队列中选择了乳酸代谢和转运相关的 21 个基因进行 LASSO cox 回归分析,最终筛选出三个基因(PNKD、SLC16A8、SLC5A8),构建了透明细胞肾细胞癌患者的临床预后模型。基于我们构建的预后模型,在 E-MTAB-1980 队列的训练集中,高风险组和低风险组的患者的超生存率(风险比=4.117,95%置信区间:1.810-9.362,p<0.0001)有显著差异,在验证集 TGCA 队列中也观察到了类似的结果(风险比=1.909,95%置信区间:1.414-2.579,p<0.0001)。使用 CIBERSORT 算法分析不同风险组中免疫细胞浸润的差异,我们发现高风险组中的树突状细胞、M1 巨噬细胞和 CD4+记忆细胞明显低于低风险组,而 Treg 细胞则高于低风险组。最后,通过基因富集分析,我们发现与预后模型密切相关的信号通路是细胞周期。