Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer
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Maider Ibarrola-Villava1, Marta J. Llorca-Cardeñosa1, Noelia Tarazona1, Cristina Mongort2, Tania Fleitas1, José Alejandro Perez-Fidalgo1, Susana Roselló1, Samuel Navarro2, Gloria Ribas1, Andrés Cervantes1
1Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain
2Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain
Gloria Ribas, e-mail: firstname.lastname@example.org
Andres Cervantes, e-mail: email@example.com
Keywords: gastric cancer, gene expression, microRNA expression, immunohistochemistry, biomarkers
Received: June 04, 2015 Accepted: July 17, 2015 Published: July 27, 2015
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.
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