Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery.
BACKGROUND
Despite well-studied tumor hypoxia in laboratory, little is known about the association with other pathophysiological events in the clinical view. We investigated the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1alpha) in hepatocellular carcinoma (HCC), and its correlations with inflammation, angiogenesis and MYC oncogene.


METHODS
In a random series of 110 HCC patients, the mRNA of HIF-1alpha, inflammation related factors (COX-2, MMP7 and MMP9), angiogenesis related factors (VEGF and PDGFRA) and MYC in tumor tissue were detected by real-time RT-PCR and HIF-1alpha protein was assessed by immunohistochemistry. The correlations between HIF-1alpha mRNA and the factors mentioned previously, the relationship between HIF-1alpha and clinicopathologic features, and the prognostic value were analyzed.


RESULTS
The expression of both HIF-1alpha mRNA and protein in HCC were independent prognostic factors for overall survival (OS) (P = 0.012 and P = 0.021, respectively) and disease-free survival (DFS) (P = 0.004 and P = 0.007, respectively) as well. Besides, the high expression of HIF-1alpha mRNA and protein proposed an advanced BCLC stage and more incidence of vascular invasion. The mRNA of HIF-1alpha had significantly positive correlations to that of COX-2, PDGFRA, MMP7, MMP9, MYC, except VEGF. In addition to HIF-1alpha, COX-2 and PDGFRA were also independent prognosticators for OS (P = 0.004 and P = 0.010, respectively) and DFS (P = 0.010 and P = 0.038, respectively).


CONCLUSIONS
HIF-1alpha in HCC plays an important role in predicting patient outcome. It may influence HCC biological behaviors and affect the tumor inflammation, angiogenesis and act in concert with the oncogene MYC. Attaching importance to HIF-1alpha in HCC may improve the prognostic and therapeutic technique.
Dai
Chen-Xin
CX
Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai, PR China. daichenxin@gmail.com
Gao
Qiang
Q
Qiu
Shuang-Jian
SJ
Ju
Min-Jie
MJ
Cai
Ming-Yan
MY
Xu
Yong-Feng
YF
Zhou
Jian
J
Zhang
Bo-Heng
BH
Fan
Jia
J
D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016271:Proto-Oncogene Proteins c-myc