Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis.
The aim of this study was to assess the significance of expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and associated proteins in pancreatic ductal adenocarcinoma (PDA) and their impact on prognosis. Expression of HIF-1alpha, vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), survivin, CD34 and Ki-67 and apoptotic cells was demonstrated by immunohistochemistry or TUNEL in 58 PDAs and 20 normal pancreatic tissue samples. Our results show positivity of HIF-1alpha, VEGF, Glut-1 and survivin in 70.7%, 77.6%, 67.2% and 84.5% of the patients with PDA, respectively, which is significantly higher than in the normal counterparts. Expression of HIF-1alpha correlated positively with VEGF and Glut-1 expression but not with survivin. Strong HIF-1alpha expression associated with decreased apoptotic index and increased intratumoral microvessel density. Higher HIF-1alpha, VEGF and Glut-1 expression significantly associated with advanced tumor stage and lymph node metastasis. Patients with high HIF-1alpha, VEGF and Glut-1 expressing tumors had a poorer overall survival. Furthermore, Cox regression analysis showed that HIF-1alpha is a prognostic marker of borderline significance while VEGF was important in predicting poor outcome. These results suggest that over-expression of HIF-1alpha may play an important role in cancer progression through up-regulation of VEGF and Glut-1 in PDA patients. HIF-1alpha and VEGF are potential candidates for predicting survival.
Sun
Hong-Cheng
HC
Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Qiu
Zheng-Jun
ZJ
Liu
Jun
J
Sun
Jing
J
Jiang
Tao
T
Huang
Ke-Jian
KJ
Yao
Min
M
Huang
Chen
C
D000328:Adult; D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; C107489:BIRC5 protein, human; D051272:Glucose Transporter Type 1; D051793:Hypoxia-Inducible Factor 1; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A