Lactic Acid Metabolism And Transporter Related Three Genes Predict The Prognosis of Patients With Clear Cell Renal Cell Carcinoma

Background: 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. Results: : 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. Subsequently, survival prediction was carried out based on the survival prognosis model we constructed. In the E-MTAB-1980 cohort, the area under ROC curve (AUC) of 1-, 3- and 5- years was 0.71, 0.72, and 0.77, respectively. The AUC of 1-, 3- and 5- years in TCGA cohort was 0.65, 0.65, and 0.63, respectively. Using CIBERSORT algorithm to analyze the differences in immune cell infiltration in different risk groups, we found that dendritic cells 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. Conclusions: : We constructed a prognostic model using lactic acid metabolism and transporter related genes, which can accurately predict the prognosis of patients. The poor prognosis of the high-risk group may be related to the regulation of cell cycle by lactic acid metabolism.