Abstract
Genetic and epigenetic alterations play an important role in gastric cancer (GC) pathogenesis. Aberrations of the phosphatidylinositol-3-kinase signaling pathway are well described. However, emerging genes have been described such as, the chromatin remodeling gene ARID1A. Our aim was to determine the expression levels of four GC-related genes, ARID1A, CDH1, cMET and PIK3CA, and 14 target-related microRNAs (miRNAs). We compared mRNA and miRNA expression levels among 66 gastric tumor and normal adjacent mucosa samples using quantitative real-time reverse transcription PCR. Moreover, ARID1A, cMET and PIK3CA protein levels were assessed by immunohistochemistry (IHC). Finally, gene and miRNAs associations with clinical characteristics and outcome were also evaluated. An increased cMET and PIK3CA mRNA expression was found in 78.0% (P = 2.20 × 10-5) and 73.8% (P = 1.00 × 10-3) of the tumors, respectively. Moreover, IHC revealed that cMET and PIK3CA expression was positive in 63.6% and 87.8% of the tumors, respectively. Six miRNAs had significantly different expression between paired-samples, finding five up-regulated [miR-223-3p (P = 1.65 × 10-6), miR-19a-3p (P = 1.23 × 10-4), miR-128-3p (P = 3.49 × 10-4), miR-130b-3p (P = 1.00 × 10-3) and miR-34a-5p (P = 4.00 × 10-3)] and one down-regulated [miR-124-3p (P = 0.03)]. Our data suggest that cMET, PIK3CA and target-related miRNAs play an important role in GC and may serve as potential targets for therapy.
Highlights
Cancer gastric (GC) is the third most common cause of cancer-related deaths [1] showing a higher incidence in Asian countries
MicroRNAs were found to play an important role in GC [6, 7]. To assess their potential deregulation in GC, we studied ARID1A, CDH1, cMET and PIK3CA expression levels in gastric adenocarcinoma comparing them with normal gastric mucosa, using quantitative real-time reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC)
Normal gastric mucosa and gastric tumor tissues were compared for ARID1A, CDH1, c-MET and PIK3CA mRNA expression using RT-qPCR
Summary
Cancer gastric (GC) is the third most common cause of cancer-related deaths [1] showing a higher incidence in Asian countries. The incidence of GC affecting some locations, in the gastroe sophageal junction, is rising in western countries. The aetio-pathogenesis of this disease remains unclear. Both environmental and genetic and epigenetic factors influence the development of the sporadic disease. Prognosis for GC remains poor due to the absence of specific biomarkers for early detection, and lack of highly specific and effective therapies
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