title: Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma.
abstract: Clear cell renal cell carcinoma (ccRCC) is an aggressive disease with unpredictable behaviour. Clinical parameters are not always accurate for prognosis prediction. The integration of molecular markers to prognostic models can significantly improve prognostic assessment and consequently patient management. We assessed the expression of alpha-enolase (ENO1) protein by immunohistochemistry in 360 patients with primary ccRCC and correlated its expression with multiple clinicopathological parameters including stage, grade, tumor size, disease-free and overall survival. Cox proportional hazard regression models adjusted for clinicopathological factors were used to test for a link between ENO1 expression and both disease-free and overall survival. We correlated ENO1 mRNA expression with overall survival in an independent set of 428 ccRCC cases from The Cancer Genome Atlas. ENO1 showed cytoplasmic, membranous and nuclear staining patterns. There is a statistically significant negative correlation between ENO1 expression, tumor stage, and grade. ENO1 expression also shows a statistically significant direct correlation with disease-free survival (p = 0.011) and overall survival (p = 0.030) in ccRCC. Patients with higher ENO1 expression had lower hazard ratio of recurrence, although this was not statistically significant (HR = 0.330, p = 0.060). These findings were validated at the mRNA level in an independent set of 428 ccRCC cases which also showed that low ENO1 expression is associated with significantly shorter overall survival. Down-regulation of ENO1 can be a predictor of poor prognosis in ccRCC, and it can be a potential prognostic marker.
authors.affiliation: Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada, nmawhite@gmail.com.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: White-Al Habeeb
authors.forename: Ashley
authors.initials: A
authors.lastname: Di Meo
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Fabio
authors.initials: F
authors.lastname: Rotondo
authors.forename: Olena
authors.initials: O
authors.lastname: Masui
authors.forename: Annetta
authors.initials: A
authors.lastname: Seivwright
authors.forename: Manal
authors.initials: M
authors.lastname: Gabril
authors.forename: Andrew H A
authors.initials: AH
authors.lastname: Girgis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jewett
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase