Evaluation of malignant and benign gastric biopsy specimens by mRNA expression profile and multivariate statistical methods.
BACKGROUND
mRNA expression array and multivariate statistical analysis of gastric biopsies can yield insight into the molecular biology basis of local alterations, supporting expression-based identification of morphological alterations.


METHODS
From 11 patients with erosive gastritis(EG), 5 with adenocarcinoma (GC), 11 with atrophic gastritis (AG) gastric biopsies were collected, total RNA isolated, T7 amplification and expression analysis of 1047 mRNAs was performed using commercial glass arrays (Clontech, USA). After microarray quality control, applicable data were available from 7 EG, 4 GC, and 5 AG. Multivariate statistical and cell functional analysis were performed. Real-time RT-PCR and immunohistochemistry were used for validation.


RESULTS
GC was characterized by overregulated v-raf, v-erb-a, BCL2-associated- athanogene, immediate-early-response-3, Polo-like kinase, CDK-2, cyclin-C, Pin1 genes, and downregulated ADP-ribosyltransferase, sialophorin and DCC. AG cases had increased PDGF-receptor, TGF-beta-receptor-3, and decreased death-associated-protein-3, beta-1-catenin, topoisomerase-1 levels. In EG upregulation of IGF-receptor-1, CD9, transferrin receptor, integrins, and underexpression of keratin-5, caspase-4 was found. Discriminant analysis could reclassify all samples correctly using four parameters.


CONCLUSIONS
mRNA expression array analysis of gastric biopsies yields previously known and new data in the evaluation of local gastric alterations.
Galamb
Orsolya
O
2nd Department of Internal Medicine, University Semmelweis, Faculty of Medicine, Budapest, Hungary. orsg@freemail.hu
Sipos
Ferenc
F
Molnar
Bela
B
Szoke
Dominika
D
Spisak
Sandor
S
Tulassay
Zsolt
Z
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D016000:Cluster Analysis; D004252:DNA Mutational Analysis / Q000379:methods; D016002:Discriminant Analysis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1