Abstract
Growing evidences showed that a large number of miRNAs were abnormally expressed in cervical cancer tissues and played irreplaceable roles in tumorigenesis, progression and metastasis. The aim of the present study was to identify the differential miRNAs expression between cervical cancer and normal cervical tissues by analyzing the high-throughput miRNA data downloaded from TCGA database. Additionally, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a three-miRNA signature that could effectively predict patient survival. According to the cut-off criteria (P < 0.05 and |log2FC| > 2.0), a total of 78 differentially expressed miRNAs were identified between cervical cancer tissues and matched normal tissues, including 37 up-regulated miRNAs and 41 down-regulated miRNAs. The Kaplan-Meier survival method revealed the prognostic function of the three miRNAs (miRNA-145, miRNA-200c, and miRNA-218-1). Univariate and multivariate Cox regression analysis showed that the three-miRNA signature was an independent prognostic factor in cervical cancer. The functional enrichment analysis suggested that the target genes of three miRNAs may be involved in various pathways related to cancer, including MAPK, AMPK, focal adhesion, cGMP-PKG, wnt, and mTOR signaling pathway. Taken together, the present study suggested that three-miRNA signature could be used as a prognostic marker in cervical cancer.
Highlights
According to the world cancer statistics, cervical cancer is the fourth most common cancer affecting women globally and the second most common cancer in developing areas[1, 2], with an estimated global incidence of 530,000 new cases and 270,000 deaths annually[3]
A total of 254 samples were enrolled in this study, including 251 cervical cancer tissues and 3 matched normal tissues
According to the cut-off criteria (P < 0.05 and |log2FC| > 2.0), a total of 78 differentially expressed miRNAs were identified between cervical cancer tissues and matched normal tissues, including 37 up-regulated and 41 down-regulated miRNAs (Table S1)
Summary
According to the world cancer statistics, cervical cancer is the fourth most common cancer affecting women globally and the second most common cancer in developing areas[1, 2], with an estimated global incidence of 530,000 new cases and 270,000 deaths annually[3]. The preventive vaccination and organized screening programs are critical in identifying the cervical cancer before it enters advanced stages. The treatments are often less effective in advanced stages compared with early interventions[4]. Understanding of the molecular mechanisms of cervical cancer development and identification of novel biomarkers are required for the early detection and treatment of cervical cancer. MicroRNAs (miRNAs), a key component of the noncoding RNA family, are approximately 18–25 nucleotides that involved in the post-transcriptional regulation of gene expression[5]. It has been shown that miRNAs are aberrantly expressed in various types of malignancies and function either as oncogenes or tumor suppressors[6]. We analyzed the pathway and function of the target genes of three miRNAs, which may provide novel insights into understanding the underlying molecular mechanism of cervical cancer
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