Identification of a three-miRNA signature as a novel prognostic model for papillary renal cell carcinoma

Ge Li,Xu Li,Xin Zhao,Yong Cheng,Haifan Yang,Rui Jiang

doi:10.1186/s12935-020-01398-2

Ge Li, Xu Li + Show 4 more

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https://doi.org/10.1186/s12935-020-01398-2

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Abstract

BackgroundPapillary renal cell carcinoma (pRCC) accounting for near 20% of renal cell carcinoma is the second most common histological subtype. MiRNAs have been demonstrated to played significant roles on predicting prognosis of patients with tumors. An appropriate and comprehensive miRNAs analysis based on a great deal of pRCC samples from The Cancer Genome Atlas (TCGA) will provide perspective in this field.MethodsWe integrated the expression of mRNAs, miRNAs and the relevant clinical data of 321 pRCC patients recorded in the TCGA database. The survival-related differential expressed miRNAs (sDEmiRs) were estimated by COX regression analysis. The high-risk group and the low-risk group were separated by the median risk score of the risk score model (RSM) based on three screened sDEmiRs. The target genes, underlying molecular mechanisms of these sDEmiRs were explored by computational biology. The expression levels of the three sDEmiRs and their correlations with clinicopathological parameters were further validated by qPCR.ResultsBased on univariate COX analysis (P < 0.001), eighteen differential expressed miRNAs (DEmiRs) were remarkably related with the overall survival (OS) of pRCC patients. Three sDEmiRs with the most significant prognostic values (miR-34a-5p, miR-410-3p and miR-6720-3p) were employed to establish the RSM which was certified as an independent prognosis factor and closely correlated with OS. In the verification of clinical samples, the overexpression of miR-410-3p and miR-6720-3p were detected to be associated with the advanced T-stages, while miR-34a-5p showed the reversed results.ConclusionThe study developed a RSM based on the identified sDEmiRs with significant prognosis prediction values for pRCC patients. The results pave the avenue for establishing and optimizing a reliable and referable risk assessing model and provide novel insight into the researches of biomarkers and clinical treatment strategies.

Highlights

Papillary renal cell carcinoma accounting for near 20% of renal cell carcinoma is the second most common histological subtype
Differential expression of messenger RNAs (mRNAs) and miRNA 1244 differentially expressed Papillary renal cell carcinoma (pRCC) genes were screened by limma algorithm, of which 462 were down-regulated and 782 were up-regulated (Fig. 1a)
The relationships between differential expressed miRNAs (DEmiRs) and prognosis Based on COX Regression model, we screened 18 DEmiRs which were closely associated with the prognosis of patients with pRCC, such as miR-323a-3p, miR-409-5p, miR-34a-5p, miR-539-5p, miR-376c-3p, miR-379-5p, miR-337-3p, miR-410-3p, miR-216a-5p, miR-495-3p, miR-381-3p, miR-382-5p, miR-493-3p, miR-411-3p, miR-519a-5p, miR-6720-3p, miR-105-5p and miR-224-5p

Summary

Introduction

Papillary renal cell carcinoma (pRCC) accounting for near 20% of renal cell carcinoma is the second most common histological subtype. Food and Drug Administration (FDA) has approved certain drugs of immunotherapy and targeted therapy, and some of which gained encouraging outcomes for only a few subgroups of patients with pRCC, a wider range of pRCC patients remain in desperate need of the more ideal and promising treatment strategies [8, 9]. From another perspective, identification of more valuable biomarkers to predict the therapy response rate and prognosis will contribute to beforehand distinguish personalized patients with satisfied sensitivities and improve the whole therapeutic efficiency. With the increasingly thorough insights of the vital effects of genetics and genetic modification approaches on tumor behaviors and prognosis, researchers have been identifying the rising numbers of genetic markers including certain coding genes and non-coding genes such as long non-coding RNA (lncRNAs) and microRNAs (miRNAs) in TME, their potentials for the prediction of prognosis are awaiting to be adequately elucidated [12,13,14]

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