title: Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype: reduction during tumor progression and favorable prognosis.
abstract: Gastric cancer (GC) is one of the most common malignancies worldwide. Better knowledge of the changes in gene expression that occur during gastric carcinogenesis may lead to improvements in diagnosis, treatment and prevention. In this study, we screened for genes upregulated in GC by comparing gene expression profiles from microarray and serial analysis of gene expression and identified the HOXA10 gene. The aim of the present study was to investigate the significance of HOXA10 in GC. Immunohistochemical analysis demonstrated that 221 (30%) of 749 GC cases were positive for HOXA10, whereas HOXA10 was scarcely expressed in non-neoplastic gastric mucosa except in the case of intestinal metaplasia. Next, we analyzed the relationship between HOXA10 expression and clinicopathological characteristics. HOXA10 expression showed a significant inverse correlation with the depth of invasion and was observed more frequently in the differentiated type of GC than in the undifferentiated type of GC. HOXA10 expression was associated with GC with the intestinal mucin phenotype and correlated with CDX2 expression. Furthermore, the prognosis of patients with positive HOXA10 expression was significantly better than in the negative expression cases. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and wound healing assay revealed that knockdown of HOXA10 in GC cells by short interfering RNA transfection significantly increased viability and motility relative to the negative control, indicating that HOXA10 expression inhibits cell growth and motility. These results suggest that expression of HOXA10 may be a key regulator for GC with the intestinal mucin phenotype.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Anami
authors.forename: Htoo Zarni
authors.initials: HZ
authors.lastname: Oo
authors.forename: Naohiro
authors.initials: N
authors.lastname: Uraoka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009077:Mucins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D009077:Mucins; D012333:RNA, Messenger; C069634:HOXA10 protein, human