论文部分内容阅读
目的缺氧诱导因子-1α(hypoxia-inducible factor 1α,HIF-1α)是细胞应对缺氧时的关键转录因子,在多种恶性肿瘤中过表达。本研究系统评价HIF-1α蛋白过表达在肝细胞癌(hepatocellular carcinoma,HCC)发生、发展及患者预后中所起的作用。方法计算机检索Cochrane Library、PubMed、EMbase、中国知网、万方及维普数据库至2016-07,搜集国内外公开发表关于HIF-1α蛋白表达与HCC不同临床病理特征及预后相关性的研究。按纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,运用Stata 11.0软件进行Meta分析,应用比值比(odds ratio,OR)或风险比(hazard ratio,HR)及95%可信区间(confidence interval,CI)评价结局指标,并进行发表偏倚评估及敏感性分析。结果共纳入9个病例研究,共计1 178例患者。Meta分析结果显示,HIF-1α蛋白表达在HCC伴包膜侵犯组明显高于无包膜侵犯组(OR=1.48,95%CI为1.07~2.05,P=0.018);在HCC伴微血管浸润组明显高于无血管浸润组(OR=2.40,95%CI为1.16~5.00,P=0.019);在TNM临床分期Ⅰ~Ⅱ期组明显低于Ⅲ~Ⅳ期组(OR=0.43,95%CI为0.31~0.61,P<0.001);但在年龄≥50岁组与<50岁组(OR=0.79,95%CI为0.33~1.89,P=0.602)、男性组与女性组(OR=1.33,95%CI为0.70~2.50,P=0.381)的表达差异无统计学意义。HIF-1α过表达患者总生存期(overall survival,OS)(HR=1.73,95%CI为1.47~2.04,P<0.001)和无进展生存期(progression free survival,PFS)(HR=1.88,95%CI为1.29~2.73,P=0.001)均较短,HIF-1α过表达可促进HCC患者术后复发,增加术后死亡风险,可能是HCC的预后可能危险因素。结论 HIF-1α蛋白与HCC包膜侵犯、微血管浸润及临床分期等临床病理学特征密切相关;HIF-1α过表达预示患者预后不良。
Objective Hypoxia-inducible factor 1α (HIF-1α) is a key transcription factor when cells respond to hypoxia and is overexpressed in many malignant tumors. This study systematically evaluated the role of HIF-1α overexpression in the occurrence, development and prognosis of hepatocellular carcinoma (HCC). Methods The Cochrane Library, PubMed, EMbase, CNKI, Wanfang and VIP databases were searched by computer to 2016-07. We collected data on the relationship between HIF-1α protein expression and clinicopathologic features and prognosis of HCC. According to inclusion and exclusion criteria, the literature was screened, the data were extracted and the quality of the included studies was evaluated. Meta-analysis was performed using Stata 11.0 software. The odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CIs) were used to evaluate the outcomes and published publication bias and sensitivity analysis. Results A total of 9 case studies were included, totaling 1,178 patients. The results of Meta analysis showed that the expression of HIF-1αprotein in HCC with envelope invasion was significantly higher than that in non-envelope invasion (OR = 1.48, 95% CI 1.07 ~ 2.05, P = 0.018); in HCC with microvascular infiltration (OR = 2.40, 95% CI 1.16-5.OO, P = 0.019). In TNM clinical stage Ⅰ ~ Ⅱ group was significantly lower than that in Ⅲ ~ Ⅳ stage (OR = 0.43, 95% CI (OR = 0.79 ~ 1.89, P = 0.602), male and female groups (OR = 1.33, 95% CI 0.33 ~ 1.89, P 0. 001) % CI was 0.70 ~ 2.50, P = 0.381) the expression difference was not statistically significant. The overall survival (OS) was significantly higher in patients with HIF-1α overexpression (HR 1.73, 95% CI 1.47-2.04, P 0.001) and progression free survival (PFS) (HR 1.88, 95 % CI was 1.29-2.73, P = 0.001). HIF-1α overexpression promoted postoperative recurrence and increased postoperative mortality in HCC patients, which may be a possible risk factor for prognosis of HCC. Conclusions HIF-1α protein is closely related to HCC envelope invasion, microvascular invasion and clinicopathological features. HIF-1α overexpression indicates poor prognosis.