Gene expression changes in patient-matched gastric normal mucosa, adenomas, and carcinomas

• Published in: Experimental and molecular pathology Vol. 90; no. 2; pp. 201 - 209
• Main Authors: Kim, Hyunki, Eun, Jung Woo, Lee, Hanna, Nam, Suk Woo, Rhee, Hwanseok, Koh, Kwi Hye, Kim, Hoguen
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-04-2011; Elsevier
• Subjects: Adenoma - enzymology; Adenoma - genetics; Adenoma - pathology; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma - enzymology; Carcinoma - genetics; Carcinoma - pathology; Cluster Analysis; Down-Regulation - genetics; Female; Gastric adenoma; Gastric carcinoma; Gastric Mucosa - enzymology; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm - genetics; Humans; Hydroxyprostaglandin dehydrogenase 15; Hydroxyprostaglandin Dehydrogenases - genetics; Hydroxyprostaglandin Dehydrogenases - metabolism; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Oligonucleotide microarray; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptides - genetics; Peptides - metabolism; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Trefoil factor; Trefoil Factor-2; Tumors; Up-Regulation - genetics; Gastric carcinoma; Trefoil factor; Hydroxyprostaglandin dehydrogenase 15; Gastric adenoma; Oligonucleotide microarray; Human; Stomach; Digestive system; Enzyme; Mucosa; DNA chip; Malignant tumor; Adenoma; Gene expression; Normal; Stomach cancer; Stomach carcinoma; Anatomic pathology; Digestive diseases; Oxidoreductases; Benign neoplasm; 3α-Hydroxysteroid dehydrogenase (B-specific); Cancer; Gastric disease
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2010.12.004

A subset of gastric carcinomas shows histologic evidence of a multistep process, progressing from gastric adenoma to gastric carcinoma. We examined gene expression changes during the gastric adenoma-carcinoma sequence in 26 snap-frozen samples (normal mucosa, adenoma, and carcinoma samples from eight patients and two additional carcinomas) by oligonucleotide microarray. Unsupervised hierarchical clustering analysis demonstrated differential gene expression between gastric normal mucosa, adenomas and carcinomas.
We identified 319 and 422 genes differentially regulated in adenoma and carcinoma, respectively, relative to normal mucosa, using a combination of Welch's t-test and fold-change analysis. Applying a combination of robust multi-category support vector machines to the data, reveal that 39 and 21 genes were gradually up- and down-regulated, respectively, in succession in normal mucosa, adenoma, and carcinoma samples. We validated gene expression levels of four genes: hydroxyprostaglandin dehydrogenase 15 (HPGD), follistatin-like 1, trefoil factor 1 (TTF1) and trefoil factor 2 (TFF2) by RT-PCR and found direct correlation with microarray results. The expressions of the TFF2 and HPGD genes were further evaluated by immunohistochemistry in 103 adenomas and 70 carcinomas; expression of both proteins was decreased in these tissues. The progressive alteration in gene expression in the transition from normal mucosa to carcinoma suggests that these changes may play critical roles in gastric carcinogenesis.
► We examined gene expression changes during the gastric adenoma-carcinoma sequence. ► Patient-matched 26 snap-frozen samples were analyzed by microarray. ► We identified differentially regulated genes in adenoma and carcinoma, respectively. ► We validated expression levels of some genes by RT-PCR and immunohistochemistry.