Prognostic value of D‑lactate dehydrogenase in patients with clear cell renal cell carcinoma

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.

Prognostic Value of Lactate Dehydrogenase Expression in Different Cancers: A Meta-Analysis

“…We used a Galbraith plot to determine the main cause of heterogeneity. Heterogeneity was due to the studies of Dorneburg et al, 34 Liao et al 6 and Wang et al 1 Heterogeneity became relatively low when the articles of Dorneburg et al 34 , Liao et al 6 and Wang et al 1 were excluded (I2 = 6.1%, x2 = 11.72, P = 0.385). However, the outcome was still significant (HR = 1.66, 95%CI:…”

“…We used a Galbraith plot to determine the main cause of heterogeneity. Heterogeneity was attributed to the studies of Liao et al 6 and Wang et al 1 . Heterogeneity became relatively low when we excluded the articles of Liao et al 6 and Wang et al 1…”

“…The human genome includes 4 LDH genes, namely, LDHA, LDHB, LDHC, and LDHD. 1 LDHA is a subunit of LDH, and it mainly exists in skeletal muscles. Although most LDHA is located in the cytoplasm in a single cell, LDHA can also be found in the nucleus.…”

“…THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES VOLUME 358 NUMBER 6 DECEMBER 2019 LDH expression may improve the survival condition. 1,6,16 For instance, Koh et al 16 reported that positive LDHB expression enhances recurrence-free survival (RFS) in non-small-cell lung cancer. However, studies on this area are limited, and the complex role of LDH expression in the initiation and progression of multiple tumors is unclear.…”

Identification of microenvironment‐related genes with prognostic value in clear cell renal cell carcinoma

“…LCN2 is only expressed in the tumor microenvironment and cuts off the apoptosis signal by promoting the expression of extracellular growth factors to help cancer cells achieve immune escape, leading to tumor progression and metastasis 35 . The low expression of LDHD is also considered to be a predictor of poor prognosis for ccRCC patients 36 . However, although the result of LDHD in the ICGC database is meaningful, the conclusion is the opposite (Figure 7C).…”