The Identification of Common Potential Biomarkersand Mechanism for Two Types of Renal Cancer

Objective Renal cell carcinoma is a malignant tumor originating from the renal tubular epithelial system.In the fieldof miRNA biomarkers for renal cancer,many previous researches had ignored the large gap in the amounts of samples betweendifferent subtypes of renal cancer,this may lead to differences in the diagnostic ability of selected miRNA biomarkers amongpatients with different subtypes of renal cancer,and may cause missed diagnosis and misdiagnosis.Therefore,we considered twosubtypes of kidney cancer common markers for the study.MethodsStatistics and two machine learning methods were performedto 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 curvewas used to verify the diagnostic ability of these biomarkers,machine learning methods using external data set(KICH)were alsoconformed 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 ofmiRNA markers were investigated using bioinformatics methods.ResultsA total of6common miRNA markers for both types ofkidney cancer were obtained(miR-21,mir-210,mir-185,mir-188,mir-362,mir-199a-2),4of them have been reported to beassociated with renal cancer.Mir-188and mir-199a-2have not been reported to be associated with renal cancer,and maybe novelmiRNA biomarkers of renal cancer.Then,we performed bioinformatic analysis on these6miRNA biomarkers,the results showedthat the newly discovered biomarkers(mir-188and mir-199a-2),were involved in the regulation of two renal cancer related pathway,MAPK signaling pathway and TGF-beta signaling pathway.The differential expression of miRNA and its target genes in the pathwaywas verified,which further proved the reliability of miRNA as a marker and its regulatory effect on target genes.Also a possiblemechanism of how9target genes of mir-185(all belonging to the UGT1A gene family)participate in renal cancer was found,andthere was no related literature.ConclusionThe present study identifies possible new common miRNA markers for both types ofkidney cancer and discovers a mechanism of kidney carcinogenesis that has not been seen in kidney cancer-related fields.