Cover Story：Objective Renal cell carcinoma is a malignant tumor originating from the renal tubular epithelial system. In the field of miRNA biomarkers for renal cancer, many previous researches had ignored the large gap in the amounts of samples between different subtypes of renal cancer, this may lead to differences in the diagnostic ability of selected miRNA biomarkers among patients with different subtypes of renal cancer, and may cause missed diagnosis and misdiagnosis. Therefore, we considered two subtypes of kidney cancer common markers for the study.Methods Statistics and two machine learning methods were performed to screen the expression profile data of clear renal cell carcinoma (ccRCC, KIRC) and papillary renal cell carcinoma (pRCC, KIRP) respectively and the results were intersected to obtain common miRNA markers for both types of kidney cancer. Then, ROC curve was used to verify the diagnostic ability of these biomarkers, machine learning methods using external data set (KICH) were also conformed to these biomarkers, the two methods further proved that these miRNA biomarkers’ diagnostic ability and avoided over-fitting. The rationality of these biomarkers was also verified by existing experimental literature. The molecular mechanisms of miRNA markers were investigated using bioinformatics methods.Results A total of 6 common miRNA markers for both types of kidney cancer were obtained (miR-21, mir-210, mir-185, mir-188, mir-362, mir-199a-2), 4 of them have been reported to be associated with renal cancer. Mir-188 and mir-199a-2 have not been reported to be associated with renal cancer, and maybe novel miRNA biomarkers of renal cancer. Then, we performed bioinformatic analysis on these 6 miRNA biomarkers, the results showed that the newly discovered biomarkers (mir-188 and mir-199a-2), were involved in the regulation of two renal cancer related pathway, MAPK signaling pathway and TGF-β signaling pathway. The differential expression of miRNA and its target genes in the pathway was verified, which further proved the reliability of miRNA as a marker and its regulatory effect on target genes. Also a possible mechanism of how 9 target genes of mir-185 (all belonging to the UGT1A gene family) participate in renal cancer was found, and there was no related literature.Conclusion The present study identifies possible new common miRNA markers for both types of kidney cancer and discovers a mechanism of kidney carcinogenesis that has not been seen in kidney cancer-related fields.
