Expressions and correlation analysis of HIF-1α, survivin and VEGF in patients with hepatocarcinoma.

OBJECTIVE To investigate the expressions of HIF-1α, surviving, and VEGF in patients with hepatocarcinoma as well as the correlation analysis among them. PATIENTS AND METHODS 65 patients, who were admitted to our hospital and diagnosed as hepatocarcinoma from January 2014 to October 2015, were selected as hepatocarcinoma group, while 50 healthy cases that do not have hepatocarcinoma were selected as normal control group. The expression levels of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group and normal liver tissues of control group were detected by immunohistochemical (SP) staining method; then, the correlation among them was explored. The expression levels of HIF-1α, surviving, and VEGF protein in hepatocarcinoma tissues and corresponding normal tissues were detected by Western blot. RESULTS The positive expression rate of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 46.2%, 55.4%, and 61.5%, significantly higher than that in cancer adjacent normal liver tissues of control group which was 2%, 2%, and 2%, and the differences were statistically significant (p<0.05). The expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of patients with hepatocarcinoma were correlated with clinical stage, tumor differentiation degree and extrahepatic metastasis (p<0.05), but were not related to gender and tumor size (p>0.05). By Spearman rank correlation analysis, it could be seen that HIF-1α expression was positively correlated with VEGF protein expression in hepatocarcinoma tissues (r=0.683, p<0.05). Survivin expression was positively correlated with VEGF protein expression (r=0.717, p<0.05). There was no significant correlation between HIF-1α expression and survivin expression (p>0.05). The relative quantitative value of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 3.04±0.23, 2.26±0.31, and 2.57±0.36, significantly higher than that in cancer adjacent liver tissues of control group which was 1.07±0.17, 1.31±0.27, and 1.42±0.43, and the differences were statistically significant (p<0.05). From Western blot electrophoresis scanning, it could be seen that the expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues were higher than those in cancer adjacent normal liver tissues. CONCLUSIONS The expressions of HIF-1α, surviving, and VEGF played important roles in the occurrence, invasion, and metastasis of hepatocarcinoma. In hepatocarcinoma tissues, HIF-1α, and survivin protein expression was positively correlated with VEGF expression, but survivin protein was not related to HIF-1α expression, which indicated that HIF-1α and survivin may inhibit the apoptosis of hepatocarcinoma cells and promote tumor angiogenesis by up-regulating the expression of VEGF protein, thus accelerating the occurrence and development of hepatocarcinoma.

[1]  G. Yuan,et al.  Influences of RFA combined with TACE on the HIF-1α and EGR level of patients with primary hepatic carcinoma. , 2017, European review for medical and pharmacological sciences.

[2]  G. Chen.  The relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma. , 2017, European review for medical and pharmacological sciences.

[3]  F. Quereshy,et al.  Sa1633 Discrepancy Between Gastroenterologists' and General Surgeons' Perspectives on Repeat Endoscopy in Colorectal Cancer , 2015 .

[4]  Xile Zhou,et al.  Survivin and angiotensin-converting enzyme polymorphisms with risk of colorectal cancer: a systematic review and meta-analysis , 2015, World Journal of Surgical Oncology.

[5]  Jian Luo,et al.  Maslinic Acid Induces Mitochondrial Apoptosis and Suppresses HIF-1α Expression in A549 Lung Cancer Cells under Normoxic and Hypoxic Conditions , 2014, Molecules.

[6]  Yu Zhu,et al.  Knockdown of hypoxia-inducible factor-1 alpha reduces proliferation, induces apoptosis and attenuates the aggressive phenotype of retinoblastoma WERI-Rb-1 cells under hypoxic conditions. , 2014, Annals of clinical and laboratory science.

[7]  S. Yamada,et al.  Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer. , 2013, Surgery.

[8]  T. Park,et al.  Expression of Id-1 and VEGF in non-small cell lung cancer. , 2013, International journal of clinical and experimental pathology.

[9]  L. Bazzano,et al.  United States Women Receive More Curative Treatment for Hepatocellular Carcinoma Than Men , 2013, Digestive Diseases and Sciences.

[10]  F. Motoi,et al.  miR‐197 induces epithelial–mesenchymal transition in pancreatic cancer cells by targeting p120 catenin , 2013, Journal of cellular physiology.

[11]  R. Franco,et al.  Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer. , 2013, Oncology reports.

[12]  H. Sugihara,et al.  Angiogenesis in upper tract urothelial carcinoma associated with Balkan endemic nephropathy. , 2012, International journal of clinical and experimental pathology.

[13]  Zhao-You Tang,et al.  Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma , 2011, Clinical Cancer Research.

[14]  William M Gallagher,et al.  Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer , 2010, BMC Cancer.

[15]  M. Mccarty,et al.  Practical strategies for suppressing hypoxia-inducible factor activity in cancer therapy. , 2010, Medical hypotheses.

[16]  C. Zheng,et al.  Correlation of Hypoxia-Inducible Factor 1α with Angiogenesis in Liver Tumors After Transcatheter Arterial Embolization in an Animal Model , 2010, CardioVascular and Interventional Radiology.

[17]  L. Ellis,et al.  Targeting tumor angiogenesis with histone deacetylase inhibitors. , 2009, Cancer letters.

[18]  Wei Wang,et al.  Antitumoral Activity of Rapamycin Mediated Through Inhibition of HIF-1alpha and VEGF in Hepatocellular Carcinoma , 2009, Digestive Diseases and Sciences.

[19]  S. Assefa,et al.  Role of sex steroid receptors in pathobiology of hepatocellular carcinoma. , 2008, World journal of gastroenterology.

[20]  H. Taubert,et al.  Survivin protein expression and hypoxia in advanced cervical carcinoma of patients treated by radiotherapy. , 2007, Gynecologic oncology.

[21]  S. Fan,et al.  Regulation of Angiogenesis by Id-1 through Hypoxia-Inducible Factor-1α–Mediated Vascular Endothelial Growth Factor Up-regulation in Hepatocellular Carcinoma , 2006, Clinical Cancer Research.

[22]  M. Schindl,et al.  Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer , 2006, Breast Cancer Research and Treatment.

[23]  Xudong Tang,et al.  Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1α and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells , 2005, Molecular Cancer Therapeutics.