Clear cell renal cell carcinoma (ccRCC) is one of the deadly diseases with poor metastatic disease prognosis. There is an urgent need to explore the potential molecular markers which can improve the prognosis of the disease. Histone demethylases have emerged as a powerful tool for cancer prognosis and therapeutics during the last decade. The implications of demethylases of histone 3 lysine 4 (H3K4) in ccRCC are however unrevealed. We therefore evaluated the expression of H3K4 demethylases in ccRCC, with emphasis on their clinical significance as a prognostic marker.
Total 50 histopathological confirmed cases of ccRCC were enrolled in the study. The expression of seven H3K4 demethylases was determined by Real-Time PCR using gene specific primers and correlated with tumor stage, grade and metastasis. Receiver operator characteristics (ROC) curve analysis was performed to evaluate the prognostic significance of H3K4 demethylases.
The median age of the patients was 54 years with predominance of male patients by 2.6-fold. Among seven genes viz FBXL10, LSD1, LSD2, KDM5A, KDM5B, KDM5C and KDM5D analyzed, LSD2 was found to be significantly associated with tumor stage and metastasis. The optimal cut-off value for LSD2 was 3.2 as calculated from ROC curve analysis for metastasis as well as TNM stage with area under curve of 0.74 and 0.78 respectively. In addition, LSD2 expression showed significant positive correlation with LSD1 expression in tumor metastasis.
The expression of LSD2 was associated with higher TNM stage and metastasis of the tumor and thus, might serve as a useful marker for ccRCC progression.
Gene. 2020 Feb 22 [Epub ahead of print]
Aman Kumar, Niti Kumari, Nayudu Nallabelli, Ujjawal Sharma, Ashutosh Rai, Shrawan Kumar Singh, Nandita Kakkar, Rajendra Prasad
Department of Biochemistry, Postgraduate of Institute of Medical Education and Research, Chandigarh, India., Department of Endocrinology, Postgraduate of Institute of Medical Education and Research, Chandigarh, India., Department of Neurosurgery, Postgraduate of Institute of Medical Education and Research, Chandigarh, India., Department of Urology, Postgraduate of Institute of Medical Education and Research, Chandigarh, India., Department of Histopathology, Postgraduate of Institute of Medical Education and Research, Chandigarh, India., Department of Biochemistry, Postgraduate of Institute of Medical Education and Research, Chandigarh, India. Electronic address: .