Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis.
OBJECTIVE
Macrophage migration inhibitory factor (MIF) is implicated in tumorigenesis. This study was conducted to determine whether MIF expression is associated with gastric pathology and whether MIF expression is increased in malignant gastric cells in vitro.


METHODS
Patients with a normal gastric mucosa, Helicobacter pylori infected gastritis, intestinal metaplasia, and gastric adenocarcinoma were included. Immunohistochemistry and enzyme linked immunosorbent assay (ELISA) were used to determine MIF expression in gastric epithelial cells and MIF levels in serum, respectively. Five gastric cancer cell lines (AGS, MKN-45, MKN-28, MGC-803, and SGC-7901) and one non-malignant gastric cell line (GES-1) were cultured for 24 hours. MIF protein in the supernatant and MIF mRNA in cultured cells were measured by ELISA and reverse transcription-polymerase chain reaction, respectively.


RESULTS
The percentage of MIF expressing epithelial cells was low in normal mucosa (12%) but substantially higher in gastritis (52%), intestinal metaplasia (66%), and gastric cancer (96%) (p<0.001, ANOVA). Serum MIF levels were low in patients with a normal mucosa (576 (82) pg/ml) but higher in patients with gastritis (2100 (349) pg/ml), intestinal metaplasia (4498 (253) pg/ml), and gastric cancer (9737 (1249) pg/ml) (p<0.001, ANOVA). There was a correlation between epithelial MIF expression and serum MIF levels (r = 0.776, p<0.001). In vitro, expression of MIF protein and mRNA was increased in malignant cells compared with non-malignant cells.


CONCLUSIONS
Epithelial and serum MIF expression was progressively increased in H pylori induced gastritis, intestinal metaplasia, and gastric cancer, suggesting that MIF is involved in gastric carcinogenesis and may be a valuable biomarker for the early detection of gastric cancer.
Department of Gastroenterology, The Second Affiliated Hospital of Guanzhou Medical College, Guangzhou, China.
X-X
XX
He
J
J
Yang
Y-W
YW
Ding
W
W
Liu
Q-Y
QY
Shen
H H-X
HH
Xia
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002908:Chronic Disease; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000378:metabolism*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D008263:Macrophage Migration-Inhibitory Factors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm