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

Molecular Cancer

Research

Andreas Scorilas¹  Olena Masui²  KW Michael Siu²  Andrew Evans³  Emily R Filter⁴  Manal Gabril⁴  Georg A Bjarnason⁵  Michael AS Jewett⁶  Fabio Rotondo⁷  Andrew HA Girgis⁷  Hala Girgis⁷  Annetta Seivwright⁷  George M Yousef⁸  Sahar Al-Haddad⁸  Nicole MA White⁸ 

[1] Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, 15701, Athens, Greece;Department of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele Street, M3J 1P3, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, M5S 1A8, Toronto, Canada;Department of Laboratory Medicine, University Health Network, Toronto, Canada;Department of Pathology, London Health Sciences Center and Western University, N6A 5 W9, London, Canada;Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Center, ON M4N 3 M5, Toronto, Canada;Division of Urologic Oncology, Princess Margaret Hospital, University Health Network, ON M5G 2 M9, Toronto, Canada;The Keenan Research Center in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, M5B 1 W8, Toronto, Canada;Department of Laboratory Medicine, St. Michael’s Hospital, M5B 1 W8, Toronto, Canada;The Keenan Research Center in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, M5B 1 W8, Toronto, Canada;Department of Laboratory Medicine, St. Michael’s Hospital, M5B 1 W8, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, M5S 1A8, Toronto, Canada;

关键词: Lactate dehydrogenase A;    Prognosis;    Renal cell carcinoma;    Personalized medicine;    Tumor markers;    Proteomics;    Pathology;    Metastasis;   

DOI  :  10.1186/1476-4598-13-101

 received in 2014-02-20, accepted in 2014-04-22,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Girgis et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.