Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma

Abstract

BackgroundOver 90% of cancer-related deaths in clear cell renal cell carcinoma (RCC) are caused by tumor relapse and metastasis. Thus, there is an urgent need for new molecular markers that can potentiate the efficacy of the current clinical-based models of prognosis assessment. The objective of this study is to evaluate the potential significance of lactate dehydrogenase A (LDHA), assessed by immunohistochemical staining, as a prognostic marker in clear cell renal cell carcinoma in relation to clinicopathological features and clinical outcome.MethodsWe assessed the expression of LDHA at the protein level, by immunohistochemistry, and correlated its expression with multiple clinicopathological features including tumor size, clinical stage, histological grade, disease-free and overall survival in 385 patients with primary clear cell renal cell carcinoma. We also correlated the LDHA expression with overall survival, at mRNA level, in an independent data set of 170 clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases. Cox proportional hazards models adjusted for the potential clinicopathological factors were used to test for associations between the LDHA expression and both disease-free survival and overall survival.ResultsThere is statistically significant positive correlation between LDHA level of expression and tumor size, clinical stage and histological grade. Moreover, LDHA expression shows significantly inverse correlation with both disease-free survival and overall survival in patients with clear cell renal cell carcinoma. Our results are validated by examining LDHA expression, at the mRNA level, in the independent data set of clear cell renal cell carcinoma cases from The Cancer Genome Atlas databases which also shows that higher lactate dehydrogenase A expression is associated with significantly shorter overall survival.ConclusionOur results indicate that LDHA up-regulation can be a predictor of poor prognosis in clear cell renal cell carcinoma. Thus, it represents a potential prognostic biomarker that can boost the accuracy of other prognostic models in patients with clear cell renal cell carcinoma.

Upregulated immune checkpoint HHLA2 in clear cell renal cell carcinoma: a novel prognostic biomarker and potential therapeutic target

“…Since ccRCC display a broad range of clinical features and malignancies, prognostic biomarkers are required to stratify patients and predict response to therapies. Various types of biomarkers have been proposed by independent studies as prognostics biomarkers including mRNAs,39 40 circRNAs,41 lncRNAs42 and genes 21. However, none of them have proven its suitability and accuracy for being ccRCC prognosis biomarker.…”

2ME2 inhibits the activated hypoxia-inducible pathways by cabozantinib and enhances its efficacy against medullary thyroid carcinoma

“…In hypoxic MTC cells, HIF-1 plays a major role in regulating hypoxia-inducible pathways and the expression of HGF [15], MET [7], VEGF [12], and LDHA [11]. LDHA is a key glycolytic enzyme for the conversion of glucose to lactate as the energy metabolism of cancer cells relies on glycolysis under hypoxia [31]. HIF-2 regulates the expression of cyclin D1 [21], but plays a subordinate role in regulating hypoxic response in hypoxic MTC cells.…”

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

“…Many studies in tumors confirms the view that target LDHA may represent novel therapeutic strategies for controlling tumor growth [9,10,12,[15][16][17] . Meanwhile, previous reports showed that the expression of LDHA was abnormality abundant in RCC than that in matched normal renal tissue [2,20] , which promotes us to determine the function of LDHA on renal cancer development. Consistent with previous theory, our results showed that LDHA silence with siRNA inhibit cell growth and induce cell apoptosis.…”

“…In pancreatic cancer, reduced c-myc-LDHA signaling resulted in decreased tumor growth and metastasis [18] . In clear cell RCC, previous studies showed that the expression of LDHA is upregulated compared to normal renal tissue [20] , and furthermore, many studies have the view that targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches [2,21] . However, the molecular function of LDHA in RCC, and its possible mechanism, remains unclear.…”