Identification of subtype specific biomarkers of clear cell renal cell carcinoma using random forest and greedy algorithm

Suitable biomarkers can be good indicator for cancer subtype. To find biomarkers that can accurately distinguish clear cell renal cell carcinoma (ccRCC) subtypes, we first determined ccRCC subtypes based on the expression of mRNA, miRNA and lncRNA, named clear cell type 1 (ccluster1) and 2 (ccluster2), using three unsupervised clustering algorithms. Besides being associated with the expression pattern derived from the single type of RNA, the differences between subtypes are relevant to the interactions between RNAs. Then, based on ceRNA network, the optimal combination features are selected using random forest and greedy algorithm. Further, in survival-related sub-ceRNA, competing gene pairs centering on miR-106a, miR-192, miR-193b, miR-454, miR-32, miR-98, miR-143, miR-145, miR-204, miR-424 and miR-1271 can also well identify ccluster1 and ccluster2 with prediction accuracy over 92%. These subtype-specific features potentially enhance the accuracy with which machine learning methods predict specific ccRCC subtypes. Simultaneously, the changes of miR-106 and OIP5-AS1 affect cell proliferation and the prognosis of ccluster1. The changes of miR-145 and FAM13A-AS1 in ccluster2 have an effect on cell invasion, apoptosis, migration and metabolism function. Here miR-192 displays a unique characteristic in both subtypes. Two subtypes also display notable differences in diverse pathways. Tumors belonging to ccluster1 are characterized by Fc gamma R-mediated phagocytosis pathway that affects tissue remodeling and repair, whereas those belonging to ccluster2 are characterized by EGFR tyrosine kinase inhibitor resistance pathway that participates in regulation of cell homeostasis. In conclusion, identifying these gene pairs can shed light on therapeutic mechanisms of ccRCC subtypes.