Abstract

Background

   Recent studies have extensively investigated the roles of miR-106 in
   colorectal cancer (CRC). However, the associations and molecular
   mechanism underlying the roles of miR-106 in CRC remain unclear. We
   aimed to thoroughly investigate the biomarker roles of miR-106 for
   predicting the risk and survival outcome in CRC.

Methods

   We first conducted a comprehensive meta-analysis to quantitatively
   evaluate the roles of miR-106 in the diagnosis and prognosis of CRC.
   Then, we qualitatively explored the biomarker roles of miR-106 in CRC
   through an integrative bioinformatics analysis.

Results

   The results indicated that miR-106 yielded a combined AUC of 0.79 (95%
   CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68)
   and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating
   CRC cases from normal controls. Moreover, patients with higher
   expression of miR-106 were significantly associated with shorter
   disease-free survival (HR: 1.73; 95%CI: 1.23–2.44) and overall survival
   (HR: 1.39; 95%CI: 1.09–1.77). Finally, gene ontology and pathway
   analysis demonstrated that miR-106 family was highly involved in the
   initiation and progression of CRC and indicated the potential molecular
   mechanism for miR-106 in CRC.

Conclusions

   Our results indicated that miR-106 showed promising potential as
   diagnostic and prognostic biomarker for CRC. Nevertheless, the
   underlying molecular mechanism of miR-106 family involved in CRC
   requires further investigation.

   Keywords: Colorectal cancer, Biomarker, Meta-analysis, Bioinformatics

Background

   Colorectal cancer (CRC) remains as one of most prevalent malignancies
   in both developed and developing countries, and it has become a global
   public health concern due to high mortality [[35]1]. As early symptoms
   of CRC patients are not typical, most of the CRC cases occur in locally
   advanced stages when the overall 5-year survival rate are very low.
   Although a series of predictive methods for diagnosis and prognosis of
   CRC are available, their clinically application values are limited due
   to high costs, lack of sensitivity or inconvenience [[36]2]. Thus, new,
   invasive and more specific methods for early detection and survival
   prediction are necessary to improve the survival status for CRC
   patients [[37]3].

   MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which
   play fundamental roles in regulating gene expression through inhibiting
   mRNA translation or inducing degradation of the mRNA, and then
   participate in a wide variety of key physiological processes including
   cell growth, differentiation, invasion and metastasis [[38]4]. In
   recent years, numerous studies have suggested that miRNAs may provide a
   new idea as biomarkers for tumor diagnosis, prognosis and prediction of
   efficacy [[39]5]. As one of the most common studied miRNA biomarkers,
   miR-106 has gained great attention as a novel biomarker in cancer
   detection and survival prediction [[40]6]. Several studies have
   previously indicated that miR-106 could be specifically used as a
   promising diagnostic marker for distinguishing CRC patients from normal
   subjects [[41]7]. Moreover, miR-106 expression level seems to be
   correlated with CRC patient survival [[42]8]. Nevertheless, different
   confounding factors, such as sample sources, sample sizes, detection
   methods, may result in inconsistent and conflicting conclusions.
   Moreover, the pathological mechanisms of miR-106 involved in CRC are
   still not fully understood.

   Therefore, this study aimed to quantitatively determine the potential
   biomarker value of miR-106 family and provide a more comprehensive and
   reliable conclusion on the relationship between miR-106 expression and
   the diagnosis and prognosis of CRC; in addition, an integrated
   bioinformatics was performed for uncovering the biomarker functions of
   miR-106 family at the systems biology level.

Methods

Search strategy

   Relevant studies published before May 20, 2019 were screened through a
   search in PubMed, EMBASE, Web of Science, and Cochrane Library
   databases using the following terms: (“colorectal” or “rectal” or
   “rectum” or “colon” or “CRC”) and (“cancer”, “carcinoma”, “tumor”,
   “neoplasm”) and (“microRNA-106” or “miRNA-106” or “miR-106” or
   “miRNA106”). In addition, we manually examined the references from