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

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• 作者：Hala Girgis (5) (6)
  Olena Masui (7)
  Nicole MA White (5) (6) (8)
  Andreas Scorilas (9)
  Fabio Rotondo (5) (6)
  Annetta Seivwright (5) (6)
  Manal Gabril (10)
  Emily R Filter (10)
  Andrew HA Girgis (5) (6)
  Georg A Bjarnason (11)
  Michael AS Jewett (12)
  Andrew Evans (13) (8)
  Sahar Al-Haddad (5) (6) (8)
  KW Michael Siu (7)
  George M Yousef (5) (6) (8)
  
  5. The Keenan Research Center in the Li Ka Shing Knowledge Institute ; St. Michael鈥檚 Hospital ; Toronto ; M5B 1聽W8 ; Canada
  6. Department of Laboratory Medicine ; St. Michael鈥檚 Hospital ; Toronto ; M5B 1聽W8 ; Canada
  7. Department of Chemistry and Centre for Research in Mass Spectrometry ; York University ; 4700 Keele Street ; Toronto ; M3J 1P3 ; Canada
  8. Department of Laboratory Medicine and Pathobiology ; University of Toronto ; Toronto ; M5S 1A8 ; Canada
  9. Department of Biochemistry and Molecular Biology ; Faculty of Biology ; University of Athens ; 15701 ; Athens ; Greece
  10. Department of Pathology ; London Health Sciences Center and Western University ; London ; N6A 5聽W9 ; Canada
  11. Division of Medical Oncology and Hematology ; Sunnybrook Odette Cancer Center ; Toronto ; ON M4N 3聽M5 ; Canada
  12. Division of Urologic Oncology ; Princess Margaret Hospital ; University Health Network ; Toronto ; ON M5G 2聽M9 ; Canada
  13. Department of Laboratory Medicine ; University Health Network ; Toronto ; Canada
  
• 关键词：Lactate dehydrogenase A ; Prognosis ; Renal cell carcinoma ; Personalized medicine ; Tumor markers ; Proteomics ; Pathology ; Metastasis
• 刊名：Molecular Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：460 KB
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• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

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.