Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer.
We previously cloned human G protein gamma 7 (GNG7) and demonstrated that it was downregulated in gastrointestinal cancer. The significance of GNG7 expression in oesophageal cancer is unknown. TaqMan quantitative real-time PCR was performed to determine the clinical significance of GNG7 expression in 55 cases of oesophageal cancer. Furthermore, GNG7-transfected oesophageal cancer cells were analysed in laboratory studies at genomic and epigenetic levels. Twenty-seven patients with low GNG7 expression showed significantly poorer survival than did 28 patients with high expression (P<0.05). Tumours with low GNG7 expression invaded deeper than those with high GNG7 expression (P<0.05), both in vivo and in vitro. Eight tumours retained GNG7 expression, and they did not show either promoter hypermethylation or loss of heterozygosity (LOH). In 38 tumours with GNG7 suppression, 22 (57%) showed either LOH or promoter hypermethylation. In addition, GNG7 expression was significantly associated with the presence of miR328 in oesophageal cancer cell lines, which suggests that this microRNA might be a regulator of GNG7 expression. GNG7 suppression represents a new prognostic indicator in cases of oesophageal cancer. GNG7 might be suppressed by LOH and promoter hypermethylation or by microRNA.
Ohta
M
M
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Mimori
K
K
Fukuyoshi
Y
Y
Kita
Y
Y
Motoyama
K
K
Yamashita
K
K
Ishii
H
H
Inoue
H
H
Mori
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002888:Chromosomes, Human, Pair 19; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; C527544:GNG7 protein, human; D044388:GTP-Binding Protein gamma Subunits; D035683:MicroRNAs; D012333:RNA, Messenger; D001374:Azacitidine