1. Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma
- Author
-
Annetta Seivwright, Andreas Scorilas, Michael A.S. Jewett, Andrew H. A. Girgis, George M. Yousef, Nicole M.A. White, Hala Girgis, Manal Y. Gabril, Andrew Evans, K. W. Michael Siu, Fabio Rotondo, Olena Masui, Sahar Al-Haddad, Georg A. Bjarnason, and Emily Filter
- Subjects
Male ,Proteomics ,Oncology ,Cancer Research ,Metastasis ,0302 clinical medicine ,Renal cell carcinoma ,Pathology ,Precision Medicine ,0303 health sciences ,education.field_of_study ,Prognosis ,Kidney Neoplasms ,Tumor Burden ,3. Good health ,Gene Expression Regulation, Neoplastic ,Isoenzymes ,Tumor markers ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Molecular Medicine ,Female ,medicine.medical_specialty ,Lactate dehydrogenase A ,Biology ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,Carcinoma ,medicine ,Humans ,RNA, Messenger ,education ,Carcinoma, Renal Cell ,Survival analysis ,Neoplasm Staging ,030304 developmental biology ,L-Lactate Dehydrogenase ,Proportional hazards model ,Research ,medicine.disease ,Survival Analysis ,Personalized medicine ,Clear cell renal cell carcinoma ,Lactate Dehydrogenase 5 ,Neoplasm Grading - Abstract
Background Over 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. Methods We 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. Results There 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. Conclusion Our 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.
- Full Text
- View/download PDF