Helicobacter pylori and antrum erosion-specific gene expression patterns: the discriminative role of CXCL13 and VCAM1 transcripts.
OBJECTIVE
Chronic Helicobacter pylori infection affects approximately half of the world, leads to chronic gastritis and peptic ulceration, and is linked to gastric carcinoma. Our aims were to compare the gene expression profile (GEP) of H. pylori-positive and H. pylori-negative gastric erosions and adjacent mucosa to explain the possible role and response to H. pylori infection and to get erosion-related mRNA expression patterns.


METHODS
Total RNA was extracted, amplified, and biotinylated from gastric biopsies of patients with H. pylori-positive and H. pylori-negative antrum erosions (ER) (8/8) and adjacent macroscopically normal mucosae (8/8). The GEP was evaluated using HGU133plus2.0 microarrays. Two independent normalizations (MAS5.0, RMA), PAM feature selection, hierarchical cluster analysis, and discriminant analysis were done. The expression of 14 genes was also measured by real-time-polymerase chain reaction. VCAM-1 and CXCL13 immunohistochemistry (IHC) was done.


RESULTS
In H. pylori infection, significant overexpression of MHC class II antigen-presenting genes, interleukin-7 receptor, ubiquitin-D, CXCR4, lactoferrin immune response-related genes, CXCL-2 and -13, CCL18 chemokine ligand, and VCAM-1 genes were established. In erosive gastritis, increased proliferation (MET) and transport (UCP2, SCFD1, KPNA4) were found, while genes associated with adhesion (SIGLEC11), transcription regulation (ESRRG), and electron and ion transport (ACADM, CLIC6) were down-regulated. Discriminant analysis successfully classified all samples into four groups (HP+ER-, HP+ER+, HP-ER+, HP-ER-) using a reduced gene set (20). Significant overexpression of VCAM-1 and CXC13 protein was detected by IHC in HP+ samples (p < .05).


CONCLUSIONS
Whole genomic microarray analysis yielded new H. pylori infection and erosion-related gene expression changes. Discriminative genes can be used in mRNA-based diagnostic classification of gastric biopsies.
Galamb
Orsolya
O
2nd Department of Medicine, Semmelweis University, Budapest, Hungary. orsg1@yahoo.com
Gyõrffy
Balázs
B
Sipos
Ferenc
F
Dinya
Elek
E
Krenács
Tibor
T
Berczi
Lajos
L
Szõke
Dominika
D
Spisák
Sándor
S
Solymosi
Norbert
N
Németh
Anna Mária
AM
Juhász
Márk
M
Molnár
Béla
B
Tulassay
Zsolt
Z
D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism*; D005753:Gastric Mucosa / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D011706:Pyloric Antrum; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D012329:RNA, Bacterial; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1