Circular RNA as a biomarker for cancer: A systematic meta‑analysis

Abstract

Abstract. Circular RNAs (circRNAs) may serve as biomarkers for a potentially non-invasive diagnosis of cancer. To understand their diagnostic performance, a systematic meta-analysis of the published literature was conducted to review the diagnostic efficiency of circRNAs in patients with cancer. Eligible studies published up to November 30, 2017, on PubMed and EMBASE, were selected for the meta-analysis. All studies were carefully and independently reviewed by two researchers based on their titles and abstracts, following which full texts were perused for potential eligibility. All statistical analyses were performed by STATA 13.0 statistical software and Meta-DiSc 1.4. A total of 10 eligible studies were included. The pooled diagnostic odds ratio was 7.265. The pooled sensitivity was 0.708 and the pooled specificity was 0.722. The positive likelihood and negative likelihood ratios were 2.483 and 0.372, respectively. The area under the curve was 0.793. circRNA was determined to be a notably effective assistant diagnostic biomarker for cancer. IntroductionCancer is a major public health problem globally. Cancer is a class of diseases that undergoes uncontrollable cell proliferation and differentiation. Based on the 2015 cancer statistics, it is currently the second leading cause of mortality in numerous countries (including China, Europe and the USA), and is expected to surpass heart diseases as the leading cause of mortality in the near future (1). Although the risk of succumbing to cancer has decreased by ~20% from its maximum in 1991-2011 (1), it must be diagnosed with high sensitivity and specificity in order to determine the appropriate therapy and prognosis. Recently, a number of biomarkers with diagnostic and prognostic potential value have been demonstrated in numerous cancer types, including the tumor markers human epididymis secretory protein 4 and cancer antigen 125 in endometrial (2) and ovarian cancer types (3). Additionally, mutant genes have been used in the selection of an appropriate therapy, including epidermal growth factor receptor mutation in non-small cell lung cancer (4), Kirsten rat sarcoma viral oncogene homolog in colorectal cancer (5) and v-raf murine sarcoma viral oncogene homolog B1 mutation in melanoma (6); however, reliable and convenient biomarkers are required to evaluate the diagnostic and prognostic significance of different cancer types.Classic biomarkers present with potentially limiting factors, including cost, availability and reproducibility (7). Utility is compromised by different disease heterogeneities, specific genetics and proteomics, and the influence of lifestyle; therefore, a number of serum or tissue biomarkers, including non-coding RNAs (ncRNAs), have been developed for clinical experiments. ncRNAs have notable potential for future biomarker approaches. Numerous studies have reported the use of ncRNAs, including microRNAs and long ncRNAs (lncRNAs), in the early detection and prognosis of various cancer types (8,9). Previously, a number of studies focused on a nove...

Silencing circular RNA UVRAG inhibits bladder cancer growth and metastasis by targeting the microRNA‐223/fibroblast growth factor receptor 2 axis

“…Circular RNA (circRNA) is a novel class of competitive endogenous RNAs formed by a covalently closed loop . Increasing evidence has shown that circRNAs are effective diagnostic biomarkers for some cancers .…”

“…Circular RNA (circRNA) is a novel class of competitive endogenous RNAs formed by a covalently closed loop. 4,5 Increasing evidence has shown that circRNAs are effective diagnostic biomarkers for some cancers. 6,7 Previous studies reported that abnormal expressions of circRNAs were useful to determine the progress of BLCA, and high throughput sequencing found that hsa_circ_0023642 (cir-cUVRAG) was significantly increased in BLCA.…”

Prognostic and diagnostic value of circRNAs expression in colorectal carcinoma: a meta-analysis

“…In previous meta-analysis, only five meta-analysis [32][33][34][35][36] detected the association between the circRNAs and carcinoma. However, in the studies of wang et al, Chen et al and Li et al [32,33,34], only one study was included to investigate the relationship between the circRNAs and CRC.…”

“…However, in the studies of wang et al, Chen et al and Li et al [32,33,34], only one study was included to investigate the relationship between the circRNAs and CRC. Li et al and Ding et al [35,36] assessed the diagnosis value of circRNAs for human cancers, in which five articles were included to investigate the diagnostic value of circRNAs for CRC, whereas they failed to discuss the role of circRNAs for CRC patients. In the present study, we collected all the relevant articles published to date and performed the meta-analysis including nineteen articles in 1307 CRC patients.…”

circPIP5K1A serves as a competitive endogenous RNA contributing to ovarian cancer progression via regulation of miR‐661/IGFBP5 signaling

“…Studies have proposed a hypothesis known as the competitive endogenous RNA (ceRNA) mechanism suggesting that transcripts including pseudogenes, long noncoding RNAs, and messenger RNAs (mRNAs) function as natural microRNA (miRNA) sponges via competitive binding to miRNA response elements to suppress their function and expression. In tumors, circRNAs appear to act as antagonists of specific miRNAs by functioning as miRNA sponges . Previous investigations reported uncommon expressions of circRNAs in association with the development of different cancer types, such as bladder cancer, hepatocellular carcinomas, non–small cell lung cancer, breast cancer, and ovarian cancer …”