Abstract

Background

   Recently, accumulating evidences have revealed that microRNA-106
   (miR-106) may serve as a non-invasive and cost-effective biomarker in
   gastric cancer (GC) detection. However, inconsistent results have
   prevented its application to clinical practice.

Methods

   As a result of this, a comprehensive meta-analysis was conducted to
   evaluate the diagnostic performance of miR-106 alone and
   miR-106-related combination markers for GC detection. Meanwhile, an
   integrative bioinformatics analysis was performed to explore the
   function of miR-106 at the systems biology level.

Results

   The results in our work showed that sensitivity of 0.71 (95% CI
   0.65–0.76) and specificity of 0.82 (0.72–0.88), with the under area AUC
   (area under the curve) value of 0.80 (0.76–0.83) for miR-106 alone.
   Prospectively, miR-106-related combination markers improved the
   combined sensitivity, specificity and AUC, describing the
   discriminatory ability of 0.78 (0.65–0.87), 0.83 (0.77–0.89) and 0.88
   (0.85–0.90) in the present analysis. Furthermore, targets of miR-106
   were obtained and enriched by gene ontology and Kyoto Encyclopedia of
   Genes and Genomes pathway analysis, revealing their associations with
   the occurrence and development of GC. Hub genes and significant modules
   were identified from the protein–protein interaction networks
   constructed by miR-106 targets and found closely associated with the
   initiation and progression of GC again.

Conclusions

   Our comprehensive and integrative analysis revealed that miR-106 may be
   suitable as a diagnostic biomarker for GC while microRNA combination
   biomarkers may provide a new alternative for clinical application.
   However, it is necessary to conduct large-scale population-based
   studies and biological experiments to further investigate the
   diagnostic value of miR-106.

   Keywords: Gastric cancer, Meta-analysis, System biological analysis,
   Diagnosis

Background

   Gastric cancer (GC), a major public health challenge, is one of the
   leading causes of cancer death worldwide [[35]1]. There are limited
   detection methods for early diagnosis and few effective screening
   procedures in some countries. The most reliable program for diagnosis
   is mainly based on endoscopy and biopsy [[36]2]. However, this is
   invasive and inconvenient for patients to undergo. Consequently, most
   patients can only be diagnosed precisely in advanced stages when the
   clinical outcomes are poor [[37]3]. Therefore, there is a great need to
   explore new accurate and efficient, preferentially non-invasive,
   markers for early detection of GC.

   In recent time, accumulating evidences have suggested that microRNAs
   may serve as novel biomarkers for cancer detection. MicroRNAs are a
   class of small non-coding RNAs with intermediate posttranscriptional
   regulation of the target genes [[38]4]. A large number of studies have
   demonstrated that microRNAs play vital roles in a wide variety of
   physiological processes including cancer cell growth, differentiation,
   invasion, and metastasis [[39]5]. Moreover, a number of studies have
   indicated that circulating microRNAs have high degree of stability and
   tolerance even under unfavorable physiochemical conditions including
   extreme variations in pH, temperature and freeze–thaw cycles [[40]6].
   It is also promising that microRNAs have outstanding stability in
   multiple clinical samples including plasma, serum, feces and tissue,
   which enables them to be detectable effortlessly [[41]7]. Given their
   critical involvement in the vital biological processes and perfect
   biomarker features mentioned above, microRNAs could be considered as
   good candidates for using as non-invasive markers, and the application
   of them as biomarkers for early detecting GC is viable [[42]8].

   As one of the most representative microRNA biomarkers, microRNA-106
   (miR-106) has been extensively studied by a great number of researches
   in several cancers. MiR-106 belongs to the miR-17 family, one of the
   most common studied onco-microRNA groups, which includes miRs-17, -20a,
   -20b, -93, -106a and -106b. MiR-106a is a member of the miR-106a-92
   cluster located on chromosome Xq26.2 while miR-106b is located at 7q21
   [[43]9, [44]10]. There have been several studies indicating that both
   of investigated miR-106 could be expressed in the same individuals of
   gastric tumour tissues. Several studies have previously reported that
   circulating miR-106 could specifically serve as a pivotal and promising
   biomarker for GC [[45]11]. Nevertheless, the suitability of circulating
   miR-106 in early detection and diagnosis of GC remains inconsistent due
   to different sample sizes, disease statuses, sample sources, detection
   methods, and other uncontrolled factors. Moreover, the potential
   molecular mechanism of miR-106 is still poorly understood for the
   present insufficient knowledge.

   In the present study, a comprehensive meta-analysis was performed to
   obtain a better understanding of the clinical feasibility of miR-106 as
   promising biomarker for early detection and diagnosis of GC. By
   focusing not only on a single miR-106 marker, we explored whether
   combination biomarkers based on miR-106 are more effective than
   individual miR-106. Furthermore, an integrative bioinformatics analysis
   was carried out to evaluate the functions of miR-106 at the systems
   biology level.

Methods

Literature search strategy

   A comprehensive computerized literature search for articles (up to
   December 27, 2017) was carried out based on several electronic
   databases including PubMed, EMbase, Web of Science and the Cochrane
   Library using the following search terms: (“cancer” OR “tumor’’ OR
   “carcinoma” OR “neoplasm”) AND (“gastric” OR “stomach’’ OR
   “gastrointestinal’’ OR “digestive” OR “GC”) AND (“microRNA-106” OR
   “miR-106” OR “miR-106a” OR “miR-106b”). In addition, the references of