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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

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

Authors: Hala Girgis, Olena Masui, Nicole MA White, Andreas Scorilas, Fabio Rotondo, Annetta Seivwright, Manal Gabril, Emily R Filter, Andrew HA Girgis, Georg A Bjarnason, Michael AS Jewett, Andrew Evans, Sahar Al-Haddad, KW Michael Siu, George M Yousef

Published in: Molecular Cancer | Issue 1/2014

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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.
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Metadata
Title
Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma
Authors
Hala Girgis
Olena Masui
Nicole MA White
Andreas Scorilas
Fabio Rotondo
Annetta Seivwright
Manal Gabril
Emily R Filter
Andrew HA Girgis
Georg A Bjarnason
Michael AS Jewett
Andrew Evans
Sahar Al-Haddad
KW Michael Siu
George M Yousef
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-101

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