Expression Signatures of Six-Small Nucleolar RNAs in Serum Serve as Novel Non-Invasive Biomarkers for Diagnosis and Prognosis Prediction of Renal Clear Cell Carcinoma

Abstract

Background: Small nucleolar RNAs (snoRNAs), a relatively new class of molecule, have already proved to be aberrantly expression and participate in progression in cancer. However, few related snoRNA signatures have been established for survival prediction in clear cell renal cell carcinoma (ccRCC). Methods: The snoRNA expression profiling was analyzed from TCGA database including 530 ccRCC and 72 control cases. A snoRNA-focus risk score signature was identified by multivariable Cox regression analysis. The expression of six snoRNAs in ccRCC tissues and serums were detected by qRT-PCR. Findings: We identified 43 significantly differentially expressed snoRNAs and established a six-snoRNA signature which was significantly associated with overall survival (OS) of ccRCC. The six-snoRNA signature was an independent indicator among conventional clinical factors (HR = 3.159, 95%CI = 2.238-4.461, P < 0.0001). Further ROC curve analysis revealed that this signature combined with TNM stage would have an optimal prognostic performance (AUC = 0.788). This signature also had a good accuracy and specificity in 64 clinical tissue cases and 50 serum samples. KEGG analysis indicated that this signature involved in the advanced process of ccRCC through MAPK signaling pathway and chemokine signaling pathway. Interpretation: This study identified a six-snoRNA signature as an independent and superior diagnosis and prognosis indicator for ccRCC and it exhibit promising application value in clinical practice. Funding Statement: This work was supported by National Natural Science Foundation of China and Liaoning joint fund key program (No.U1608281), Double Hundred Program for Shenyang Scientific and Technological Innovation Projects (Z18-4-020, 100040) Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: All patients consented to an institutional review board-approved protocol that allows comprehensive analysis of tumor samples (Ethics committee of the Second and Fourth Affiliated Hospitals of China Medical University and the Second Hospital of Dalian Medical University).