Relationship between clinicopathological features and HIF-2α in gastric adenocarcinoma.
Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor-2α (HIF-2α) plays an essential role in oxygen homeostasis. Expression of HIF-2α-inducible genes is associated with tumor progression. In this study, we investigated this correlation immunohistochemically and using quantitative reverse transcription-polymerase chain reaction to examine various clinical and pathological features in 55 specimens of gastric cancer and 40 specimens of normal gastric tissue. The HIF-2α mRNA expression level and protein expression were significantly higher in gastric cancer tissue samples than in adjacent tissue samples. The positive rates of HIF-2α, matrix metalloprotease-9 (MMP-9), and vascular endothelial growth factor (VEGF) protein were 63.6% (35/55), 80.0% (44/55), and 65.5% (36/55) in gastric cancer tissue specimens, respectively. These values were significantly higher than those in normal gastric tissue samples (P = 0.001, P = 0.000, and P = 0.007, respectively). HIF-2α and MMP-9 were significantly correlated with primary tumor size (P = 0.0065 and P = 0.036, respectively) and invasion depth (P = 0.012 and P = 0.008, respectively). HIF-2α and VEGF were significantly correlated with lymph node involvement (P = 0.030 and P = 0.016, respectively). Expression of HIF-2α was positively correlated with the expression of VEGF and MMP-9 (P = 0.036 and P = 0.000, respectively). These results suggest that HIF-2α is involved in gastric carcinogenesis and disease progression and is a potential therapeutic target for gastric carcinoma.
Department of Pathology, Xinxiang Medical University, Xinxiang, China lina@xxmu.edu.cn.
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N
Li
Department of Clinical Immunology, Xinxiang Medical University, Xinxiang, China.
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HX
Wang
Department of Pathology, Xinxiang Medical University, Xinxiang, China.
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C
Qin
Department of Pathology, Xinxiang Medical University, Xinxiang, China.
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XH
Wang
Department of Pathology, Xinxiang Medical University, Xinxiang, China.
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Han
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D020780:Matrix Metalloproteinase 9; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C467484:VEGFA protein, human; C579270:MMP9 protein, human