Oncotarget

Research Papers:

Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer

Maider Ibarrola-Villava, Marta J. Llorca-Cardeñosa, Noelia Tarazona, Cristina Mongort, Tania Fleitas, José Alejandro Perez-Fidalgo, Susana Roselló, Samuel Navarro, Gloria Ribas _ and Andrés Cervantes

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:26935-26945. https://doi.org/10.18632/oncotarget.4775

Metrics: PDF 1384 views  |   HTML 1450 views  |   ?  


Abstract

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

Correspondence to:

Gloria Ribas, e-mail: gribas@incliva.es

Andres Cervantes, e-mail: andres.cervantes@uv.es

Keywords: gastric cancer, gene expression, microRNA expression, immunohistochemistry, biomarkers

Received: June 04, 2015     Accepted: July 17, 2015     Published: July 27, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 4775