Abstract

Background

   It is generally accepted that microRNA-20a (miR-20a) is aberrantly
   expressed in gastrointestinal cancer (GIC), and may be associated with
   the prognosis of GIC patients. Nevertheless, the clinical prognostic
   value of miR-20a expression in GIC remains controversial.

Methods

   We first conducted a comprehensive literature search of the clinical
   data and pooled them for evidence in assessing prognostic significance
   of miR-20a expression in GIC. Afterwards, we applied some bioinformatic
   analysis methods to explore the biological function of miR-20a and
   explain why miR-20a could act as an effective biomarker.

Results

   The pooled results showed that enhanced miR-20a expression was
   significantly associated with poor survival in GIC patients (HR: 1.36;
   95%CI: 1.21–1.52; P < 0.001). According to the subgroup analysis, the
   ethnicity, cancer type, sample source, and sample size may have an
   impact on the predictive roles for miR-20a. The gene ontologies
   enriched by the predicted miR-20a targets were highly associated with
   some important biological processes, cell components and molecular
   functions. Moreover, a series of prominent pathways linked with GIC
   carcinogenesis were identified. Ultimately, the crucial targets and
   modules were identified by constructing the protein-protein interaction
   network of miR-20a targets, which were highly associated with the
   initiation and progression of GIC according to previous molecular
   biology experiments.

Conclusions

   Our results indicated that high expression of miR-20a may be a credible
   indicator of worse prognosis in GIC. Further studies involving
   biological experiments and larger sample sizes should be performed to
   validate these findings.

   Keywords: Gastrointestinal cancer, microRNA-20a, Prognosis prediction,
   Function exploration

Background

   Gastrointestinal cancer (GIC), one of the most common malignancies, has
   overtaken cardiovascular disease and infectious diseases as a
   significant health burden with the leading cause of mortality across
   the world because of the growing incidence each year and poor prognosis
   [[35]1]. Although diagnostic and therapeutic strategies for GICs have
   been greatly improved, the prognosis of these patients remains very
   unsatisfying according to the latest statistics [[36]2]. Currently, TNM
   stage-based predictive system and some markers such as CEA play
   important roles in the monitoring and prognosis of GIC. However, there
   is still no effective biological biomarkers to understand the cancer
   development and tumor behavior and promote more precise risk
   stratification, as well as optimal choice of therapy [[37]3]. Hence, it
   is urgently needed to explore new credible prognostic markers which
   could be applied to supplement the current TNM stage-based predictive
   system and to provide guidance for cancer therapy.

   The microRNAs are small single-stranded RNA molecules that mediate the
   downstream gene expression in a post-transcriptional manner [[38]4]. An
   increasing number of recent studies have emphasized the roles of
   microRNAs in a variety of biological activities such as proliferation,
   apoptosis, angiogenesis, invasion, and migration [[39]5]. Due to its
   stability and detectability in tissues and blood, microRNAs might
   function as promising biomarkers for cancer early diagnosis, prognosis
   or treatment responses prediction [[40]6].

   Notably, miR-20a stands out as the most investigated example in
   functional microRNAs. Recently published work has implicated its
   significant function in cancer pathogenesis and during the initiation
   and progression processes of carcinogenesis [[41]7]. Furthermore,
   accumulating new evidence demonstrates that aberrant expression of
   miR-20a may be highly associated with initiation and metastasis in GIC
   [[42]8]. Nevertheless, there are inconsistencies regarding the
   prognostic value of miR-20a in GIC, though a large number of studies
   reported associations between miR-20a expression and the clinical
   outcomes [[43]9].

   Thus, through a comprehensive literature search of the relevant
   studies, we conducted an integrated meta-analysis regarding the
   influence of miR-20a expression level on overall survival of GIC
   patients. Additionally, functional exploration by bioinformatic
   analysis was performed to provide a better understanding of the
   prognostic significance for miR-20a involved in the occurrence and
   development of GIC, aiming to provide more theoretical supports for
   targeted treatment.

Methods

Literature retrieval strategy

   Two researchers (QP and PZ) independently conducted a systematic
   computerized literature search for available studies in selected
   electronic databases of PubMed, EMBASE and Web of science until October
   2019. Search keywords were (microRNA-20a OR miR-20a OR miR20a OR
   miRNA-20a OR miRNA20a) AND (colorectal OR colon OR rectal OR rectum OR
   gastric OR gastrointestinal OR stomach) AND (tumor OR neoplasm OR
   cancer OR carcinoma OR malignancy). We also retrieved studies by hands
   from other potentially qualified publications to complement the results
   including relevant meta-analyses, reviews and references cited in these