Ⅰ～Ⅲ期胃癌中VEGF、 HIF-1α和TGF-β1表达的临床意义及其预后价值

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

目的探讨血管内皮生长因子(VEGF)、缺氧诱导因子1α(HIF-1α)和转移生长因子-β1(TGF-β1)在Ⅰ～Ⅲ期胃癌中的表达及其临床意义和预后价值。方法收集2004年1月至2006年12月在解放军总医院接受根治性手术且TNM分期为Ⅰ～Ⅲ期的胃癌病例。采用组织芯片及免疫组化法检测VEGF、HIF-1α和TGF-β1的表达,并分析其表达与临床病理特征及预后的关系。结果全组343例患者中,VEGF、HIF-1α和TGF-β1的阳性表达率分别为49.3%、30.9%和39.1%,且三者表达两两相关。全组患者的中位随访时间为70.0个月,至随访截止时间,出现复发或转移者232例,死亡218例,中位无疾病生存期(DFS)为23.0个月,中位生存期(OS)为31.1个月。单因素分析显示,年龄、是否全胃切除、是否含印戒细胞癌、Lauren分型、脉管癌栓、肿瘤直径、TNM分期、辅助化疗、VEGF及HIF-1α表达与DFS和OS有关(P<0.05);VEGF、HIF-1α和TGF-β1三者共阳性组的中位DFS(8.6个月)和中位OS(17.7个月)均小于双阳性、单阳性及三者共阴性组(P<0.05)。Cox多因素分析显示,是否全胃切除、是否辅助化疗、TNM分期、VEGF及HIF-1α表达均为影响DFS和OS的独立预后因素。结论对于接受根治性手术治疗的Ⅰ～Ⅲ期胃癌患者,VEGF和HIF-1α阳性表达可能是影响胃癌患者的不良预后因素。

Objective To explore the expressions of vascular endothelial growth factor（ VEGF）, hypoxia-inducible factor-1a（HIF-la） 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 diag- nosed with stage I -IU gastric cancer were collected. Paraffin-embedded samples of those cases were collected to detect expressions of VEGF, HIF-lot and TGF-β1 by immunohistochemical method and tissue chips. The expressions of VEGF, HIF-la and TGF-β1 and their relationships with clinico pathological characteristics and prognosis were analyzed. Results In a total of 343 cases, the positiveexpression rates of VEGF, HIF-1 a and TGF-β1 were 49. 3 % , 30. 9% and 39. 1% , respectively. And the expressions of VEGF, HIF- lot and TGF-I 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 intes- tinal type, negative cancer embolus, tumor diameter 〈 5cm, earlier TNM stage, received adjuvant chemotherapy, VEGF negative-ex- pression or HIF-1 negative-expression predicted better DFS and OS, respectively, compared with the matching groups for each above. In addition, all of three biomarkers （ VEGF, HIF-a, 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 biomakers negative-expressions（ P 〈 0. 05 ）, respectively. Cox multivariate analysis showed that expressions of HIF-1 a and VEGF were alsoindependent risk factors in predicting DFS and OS, after taking the TNM stage, gastrectomy method and adjuvant chemotherapy into ac- count（P 〈 0. 05 ）. Conclusion The positive-expressions of VEGF and HIF-1 a can be both considered as poor prognostic factors of DFS and OS for postoperative gastric cancer patients with stage I -Ⅲ.