Chinese Clinical Oncology

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Clinical and prognostic significances of VEGF, HIF-1α and TGF-β1 expressions for postoperative gastric cancer patients with stage Ⅰ-Ⅲ

SHI Yan, CHEN Li, WANG Zhikuan, YUAN Jing, WANG Lingxiong, DAI Guanghai.   

  1. Department of Multimodality Therapy of Oncology,Chinese PLA General Hospital
  • Received:2012-12-19 Revised:2013-02-03 Online:2013-04-30 Published:2013-04-30
  • Contact: DAI Guanghai

Abstract: Objective To explore the expressions of vascular endothelial growth factor(VEGF), hypoxiainducible factor-1 α(HIF-1α) and transforming growth factor-β1(TGF-β1) and clinical and prognostic significances in stage Ⅰ-Ⅲ postoperative gastric cancer. Methods The cases that received radical surgery in Chinese PLA General Hospital from Jan. 2004 to Dec. 2006 and diagnosed with stage ⅠⅢ gastric cancer were collected. Paraffinembedded samples of those cases were collected to detect expressions of VEGF, HIF-1α and TGF-β1 by immunohistochemical method and tissue chips. The expressions of VEGF, HIF1α and TGFβ1 and their relationships with clinico pathological characteristics and prognosis were analyzed.
Results In a total of 343 cases, the positiveexpression rates of VEGF, HIF-1α and TGF-β1 were 49.3%, 30.9% and 39.1%, respectively. And the expressions of VEGF, HIF-1α and TGF-β1 were pairwise correlated(P<0.05). After a median followup of 70.0 months, 232 patients experienced metastatic or recurrent tumors and 218 patients died. The median disease free survival(DFS) was 23.0 months and the median overall survival time(MST) was 31.1 months. Univariate analysis showed that, age<60, partial gastrectomy, without signet ring cell cancer, lauren intestinal type, negative cancer embolus, tumor diameter <5cm, earlier TNM stage, received adjuvant chemotherapy,VEGF negativeexpression or HIF1α negativeexpression predicted better DFS and OS, respectively, compared with the matching groups for each above. In addition, all of three biomarkers(VEGF, HIF-1α, TGF-β1) coexpression was significantly correlated with worse DFS(8.6 months) and OS(17.7months), compared with any two biomarkers co-expression, anyone biomarker expression or all of three biomarkers negativeexpressions(P<0.05), respectively. Cox multivariate analysis showed that expressions of HIF-1α and VEGF were also independent risk factors in predicting DFS and OS, after taking the TNM stage, gastrectomy method and adjuvant chemotherapy into account(P<0.05). ConclusionThe positiveexpressions of VEGF and HIF-1α can be both considered as poor prognostic factors of DFS and OS for postoperative gastric cancer patients with stage Ⅰ-Ⅲ.

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