Abstract
Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and is associated with the prognosis of patients with renal cell carcinoma (RCC). The human genome has four LDH genes: LDHA, LDHB, LDHC and LDHD. In order to determine which of these four LDH genes may predict clear cell RCC (ccRCC), a total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort and 192 patients with ccRCC from the Fudan University Shanghai Cancer Centre (FUSCC) cohort were enrolled in the present study. The expression profiles of LDHD genes in the TCGA cohort were obtained from the TCGA RNAseq database. The Cox proportional hazards regression model and Kaplan-Meier curves were used to assess relative factors. The LDH family genes that were revealed to have an association with overall survival (OS) were further validated in the FUSCC cohort. In the TCGA cohort, following Cox proportional hazards analysis, LDHD expression (P=0.0400; hazard ratio, 0.872; 95% confidence interval, 0.764-0.994) was revealed to be predictive of the prognosis of patients with ccRCC. Further analysis revealed that low LDHD expression (P<0.0001) was significantly associated with a poor prognosis in terms of OS. Additionally, the expression of LDHD (P<0.0001) was significantly different in patients with ccRCC compared with paired controls. In the FUSCC cohort, low LDHD expression was also associated with a poor OS (P=0.0103), and the tumour pathological T stage was a factor that influenced the expression of LDHD (P=0.0120). Furthermore, the expression of LDHD influenced the serum LDH level (P=0.0126). The downregulation of LDHD expression may be a predictor of poor prognosis in patients with ccRCC.