Otoferlin is a prognostic biomarker in patients with clear cell renal cell carcinoma: A systematic expression analysis.
OBJECTIVES
To comprehensively investigate the role of otoferlin as a prognostic and diagnostic biomarker in clear cell renal cell carcinoma.


METHODS
Three independent cohorts were used to study otoferlin in clear cell renal cell carcinoma: The Cancer Genome Atlas cohort (messenger ribonucleic acid expression; clear cell renal cell carcinoma n = 514, normal renal tissue n = 81); study validation cohort (messenger ribonucleic acid expression; clear cell renal cell carcinoma n = 79, normal renal tissue n = 44); and immunohistochemistry cohort (protein expression; clear cell renal cell carcinoma n = 142, normal renal tissue n = 30). Otoferlin gene expressions were extracted from The Cancer Genome Atlas database or determined using quantitative real-time polymerase chain reaction, respectively. Protein expression was assessed using immunohistochemistry staining against otoferlin on tissue microarrays. Correlations between otoferlin messenger ribonucleic acid/protein expression and clinicopathological data/patient survival were statistically tested.


RESULTS
Otoferlin messenger ribonucleic acid expression was significantly upregulated in clear cell renal cell carcinoma compared with normal renal tissue. High expression levels correlated with advanced stage, higher grade and metastatic tumors, accompanied by independent prognostic significance for overall and cancer-specific survival. In contrast, otoferlin protein expression was downregulated in tumor tissue. Although, high otoferlin expression in clear cell renal cell carcinoma was positively correlated with histological grading and independently predictive of a shortened progression-free survival.


CONCLUSION
Our data suggest otoferlin as an indicator of tumor aggressiveness and as a prognostic biomarker for patients with clear cell renal cell carcinoma, leading to the conclusion that otoferlin could promote the malignancy of clear cell renal cell carcinoma.
['Cox|Alexander|A|0000-0001-7837-5740', 'Tolkach|Yuri|Y|', 'Stein|Johannes|J|', 'Kristiansen|Glen|G|', 'Ritter|Manuel|M|', 'Ellinger|Jörg|J|']
D014408:Biomarkers, Tumor D002292:Carcinoma, Renal Cell D006801:Humans D007668:Kidney D007680:Kidney Neoplasms D009367:Neoplasm Staging D011379:Prognosis
otoferlin biomarker renal cell carcinoma expression analysis survival