title: Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Hala
authors.initials: H
authors.lastname: Girgis
authors.forename: Olena
authors.initials: O
authors.lastname: Masui
authors.forename: Nicole Ma
authors.initials: NM
authors.lastname: White
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Fabio
authors.initials: F
authors.lastname: Rotondo
authors.forename: Annetta
authors.initials: A
authors.lastname: Seivwright
authors.forename: Manal
authors.initials: M
authors.lastname: Gabril
authors.forename: Emily R
authors.initials: ER
authors.lastname: Filter
authors.forename: Andrew Ha
authors.initials: AH
authors.lastname: Girgis
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Michael As
authors.initials: MA
authors.lastname: Jewett
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.forename: Sahar
authors.initials: S
authors.lastname: Al-Haddad
authors.forename: Kw Michael
authors.initials: KM
authors.lastname: Siu
authors.affiliation: The Keenan Research Center in the Li Ka Shing Knowledge Institute, St, Michael's Hospital, Toronto M5B 1 W8, Canada. yousefg@smh.ca.
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D057285:Precision Medicine; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5