Research Article: A three-microRNA signature as a diagnostic and prognostic marker in clear cell renal cancer: An In Silico analysis

Date Published: June 29, 2017

Publisher: Public Library of Science

Author(s): Bin Liang, Jianying Zhao, Xuan Wang, Aamir Ahmad.

http://doi.org/10.1371/journal.pone.0180660

Abstract

Accumulating evidence has demonstrated that some specific miRNAs were aberrantly expressed in renal clear cell carcinoma and participated in many biological processes. The aim of this study was to investigate a panel of miRNA signature for diagnosis and prognosis of renal clear cell carcinoma (KIRC). Here, we performed a comprehensive analysis for miRNA expression profiles and corresponding clinical information of 516 KIRC patients from The Cancer Genome Atlas (TCGA). In the study, a total of 63 differentially expressed miRNAs were identified, of which 34 were up-regulated and 29 were down-regulated. We constructed a panel of three-miRNA that were significantly associated with KIRC diagnosis and KIRC patients’ prognosis. The three-miRNA signature reached a sensitivity of 98.3% and a specificity of 97.2% in the diagnosis of KIRC. Using the three-miRNA signature, we classified the KIRC patients into high-risk group and low-risk group. The Kaplan- Meier curves showed that KIRC patients with high risk scores had significantly worsen overall survival (OS) and disease free survival (DFS) than KIRC patients with low risk scores. In the univariate and multivariate Cox regression analysis, three-miRNA signature was an independent prognostic factor in OS. In conclusion, the three-miRNA signature could be used as a diagnostic and prognostic biomarker in KIRC, and therefore, may help to provide significant clinical implication for the treatment of KIRC.

Partial Text

Renal cell carcinoma (RCC) is the most lethal urologic cancer, accounting for 2%–3% of adult malignancies in the world [1]. More than 209,000 newly diagnosed RCC and 102,000 deaths caused by RCC are reported per year [2]. Renal clear cell carcinoma (ccRCC) is the frequently observed type of RCC (~80%), which is associated with high morbidity and poor prognosis [3]. While the interactions of environmental factors, genetic and epigenetic alterations on ccRCC development are still unclear, therapeutic options for ccRCCs are still limited [4, 5]. Therefore, understanding how the complex interactions among multiple prognostic factors contribute to the clinical behavior of ccRCC is essential for patient assessment, outcome prediction, and therapy planning.

MiRNAs are considered to be a novel group of disease biomarkers due to the stability and universality in human tissues [11, 12]. Recently, many studies have reported specific miRNA profiles in KIRC, highlighting the roles of miRNAs in the progression of KIRC [13–20]. In the present study, we comprehensively analyzed the miRNA sequencing data downloaded from TCGA datasets. Finally, we identified 63 differentially expressed miRNAs, of which 34 were up-regulated and 29 were down-regulated. We evaluated the diagnostic and prognostic values of each differentially expressed miRNA. A previous study suggested that a multiple miRNA-based signature can provide a more statistically robust analysis than individual miRNA. Accordingly, we developed a three-miRNA signature with excellent diagnostic performance and independent prognostic significance for KIRC patients.

Taken together, by performing a comprehensive analysis for differentially expressed miRNA profiles and corresponding clinical information, our study suggested that three-miRNA signature was a potential diagnostic marker in KIRC, and was an independent prognostic factor in KIRC patients. However, further studies are needed to verify our findings and establish the molecular mechanism for the interplay of miRNAs, their target genes, and KIRC progression.

 

Source:

http://doi.org/10.1371/journal.pone.0180660

 

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