Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer.
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.
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Maider
M
Ibarrola-Villava
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Marta J
MJ
Llorca-Cardeñosa
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Noelia
N
Tarazona
Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Cristina
C
Mongort
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Tania
T
Fleitas
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
José Alejandro
JA
Perez-Fidalgo
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Susana
S
Roselló
Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Samuel
S
Navarro
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Gloria
G
Ribas
Hematology and Medical Oncology Unit, Biomedical Research Institute INCLIVA, University of Valencia, 46010, Valencia, Spain.
Andrés
A
Cervantes
D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry; D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D002843:Chromatin; D058534:Class I Phosphatidylinositol 3-Kinases; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger; D014157:Transcription Factors; C112476:ARID1A protein, human; C513384:CDH1 protein, human; C484760:PIK3CA protein, human; C491743:MET protein, human
biomarkers; gastric cancer; gene expression; immunohistochemistry; microRNA expression