MicroRNA ‐ 23 a / 24 ‐ 2 / 27 a as a potential diagnostic biomarker for cancer : A systematic review and meta ‐ analysis

An increasing number of studies have proven that microRNAs play an important role in the occurrence, development and prognosis of various types of cancer. As a vital gene cluster, the microRNA (miR)-23a/24-2/27a cluster may be an important marker for predicting cancer prognosis and tumor progression. A search was conducted through PubMed, Medline and the Cochrane Library to identify studies investigating the association between the miR-23a/24-2/27a cluster and cancer, and the identified related studies were included in the present meta-analysis. The strength of the association was assessed by hazard ratio (HR) and its 95% confidence interval (95% CI). A total of 21 studies were included in this meta-analysis. The results indicated that a high level of miR‐23a exerted a significant effect on overall survival (OS) (HR=2.33, 95% CI: 1.18-4.58; P=0.014), but not on disease-free survival (DFS)/recurrence‐free survival (RFS) (HR=1.13, 95% CI: 0.37-3.44; P=0.836). There was an obvious statistically significant association between OS and the expression of miR-24 (HR=2.49, 95% CI: 1.84-3.37; P=0.000), particularly in the digestive system (pooled HR=2.99, 95% CI: 2.17-4.13, P=0.000). In addition, the result suggested a statistically significant association between the expression of miR‐27a and OS (pooled HR=1.89, 95% CI: 1.32‐2.69; P=0.001), as well as DFS/RFS/progression-free survival (HR=2.19, 95% CI: 1.29-3.70; P=0.003), particularly in renal cell carcinoma (HR=2.30, 95% CI: 1.16-4.67; P=0.017). A subgroup analysis by ethnicity, cancer type and statistical methodology was performed. There was no obvious publication bias. In conclusion, the present study demonstrated that the miR-23a/24-2/27a cluster may be a useful marker for predicting cancer prognosis and tumor progression. Introduction MicroRNAs (miRNAs, miRs) are ~22-nucleotide long, single-stranded non-coding RNA molecules (1). They were first discovered in the nematode Caenorhabditis elegans with the identification of the developmental regulator lin‐4 (2). Thus far, there are ~2,588 annotated miRNAs found in the human genome (3). With advances in research, it has been demonstrated that miRNAs may play an important role in various diseases. An increasing number of miRNAs were proven to participate in crucial biological processes, such as cell proliferation, migration, invasion and apoptosis (4-7), which may enable use of the miRNA family in the diagnosis and treatment of disease, due to the extensive alterations in miRNA expression in different diseases. miR-23a/24-2/27a encodes a ~2,159-nt pri-miRNA transcript, which is located in chromosome 19p13.12 as an intergenic miRNA cluster (8). The profiling analysis suggested that the miR‐23a/24‐2/27a cluster was significantly upregulated in hepatocellular carcinoma (HCC) (9), pancreatic adenocarcinoma (10) and breast cancer (11). There are several studies on the association of the miR-23a/24-2/27a cluster with various types of cancer. Thus, the present systematic review and meta‐analysis were designed to confirm whether miR-23a/24-2/27a may serve as a diagnostic marker for cancer. Data collection methods Literature search. Two of the authors (Jing Quan and Suyue Liu) independently conducted a search through PubMed, Medline and the Cochrane Library to identify studies on miR-23a/24-2/27a and cancer. The databases were searched from inception to September 26, 2016. In order to distinguish between miR‐24‐1 (also referred to as miR-189 and miR-24-1*) and miR-24-2 (also referred to as miR-24 precursor-19 and miR-24-2*), the miRBase was searched. The following search terms were used: (miR-23a or microRNA-23a or has-miR-23a or miR-24 or microRNA-24 or has-miR-24 or miR-27a or microRNA-27a or has-miR-27a) and (cancer or neoplasm or carcinoma or tumor). Inclusion and exclusion criteria. All the studies met the following criteria: i) They were studies on miR-23a or miR-24 MicroRNA‐23a/24‐2/27a as a potential diagnostic biomarker for cancer: A systematic review and meta‐analysis JING QUAN1,2, SUYUE LIU1,3, KANGFU DAI1,4, LU JIN1,2, TAO HE1,5, XIANG PAN1,2 and YONGQING LAI1 1Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036; 2Department of Urology, Anhui Medical University, Hefei, Anhui 230032; Departments of 3Thoracic Surgery and 4Hepatobiliary Endoscopic Surgery, Anhui Medical University, Hefei, Anhui 230032; 5Department of Urology, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China Received November 2, 2016; Accepted May 2, 2017 DOI: 10.3892/mco.2017. 1492 Correspondence to: Professor Yongqing Lai, Department of Urology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, Guangdong 518036, P.R. China E-mail: yqlord@163.com