Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications.
BACKGROUND
Hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1alpha and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival.


METHODS
Paraffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1alpha and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences.


RESULTS
Expression of HIF-1alpha and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1alpha and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (P < 0.05). Expression of both HIF-1alpha and VEGF remained significantly associated with overall survival (OS) (P < 0.01), and HIF-1alpha was positively correlative to VEGF in CRC (r = 0.72, P < 0.001).


CONCLUSIONS
HIF-1alpha and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1alpha might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.
Cao
Dan
D
Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, China. caodan316@163.com
Hou
Mei
M
Guan
Yong-song
YS
Jiang
Ming
M
Yang
Yu
Y
Gou
Hong-feng
HF
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A