缺氧诱导因子-1α蛋白表达与前列腺癌风险相关性的Meta分析

摘要

目的：系统评价缺氧诱导因子⁃1α（HIF⁃1α）蛋白表达与前列腺癌临床、病理特征及预后的关系。方法计算机检索PubMed、Cochrane图书馆、EMBASE、中国知网、维普等数据库，检索时限均截至2016年5月1日，搜集有关HIF⁃1α蛋白表达水平与前列腺癌临床、病理特征和预后关系的研究，采用RevMan 5.3软件进行Meta分析，用NOS质量评价量表对纳入文献进行评估。结果最终纳入19篇文献，共计1503例受试者，其中前列腺癌组1125例，良性前列腺增生组378例。Meta分析结果显示：HIF⁃1α蛋白表达水平前列腺癌组显著高于前列腺增生组，合并比值比=14.30（95%可信区间7.41~27.60），在Whitmore⁃Jewett临床分期中C+D期组明显高于A+B期组，合并比值比=8.51（95%可信区间4.90~14.80），TNM临床分期中Ⅲ+Ⅳ期组明显高于Ⅰ+Ⅱ期组，合并比值比=4.93（95%可信区间2.84~8.57），病理分级中低分化组明显高于高中分化组，合并比值比=5.53（95%可信区间3.74~8.18），伴淋巴结转移组明显高于无淋巴结转移组，合并比值比=7.09（95%可信区间3.87~12.98），其差异均有统计学意义。年龄大于65岁组与小于等于65岁组的对比研究发现，合并比值比=1.66（95%可信区间0.86~3.20），差异无统计学意义。HIF⁃1α蛋白表达水平对前列腺癌的无进展生存时间和无转移生存时间均有影响，合并后风险比分别为0.37（95%可信区间0.17~0.81）和9.80（95%可信区间1.50~63.86）。结论现有证据证明，HIF⁃1α参与了前列腺癌的发生、发展过程，可能是前列腺癌的一个潜在的肿瘤生物标志物。%Objective To provide a comprehensive meta⁃analysis of the extent of the possible association between hypoxia⁃inducible factor 1α(HIF⁃1α) and the risk of prostate cancer (PCa). Methods Such databases including PubMed,The Cochrane Library,EMBASE,CNKI,and VIP Database were searched from inception to May 1st 2016,for studies about the association of the clinical significance and prognostic value of HIF⁃1αexpression in PCa. Then,meta⁃analysis was performed using RevMan 5.3 software. The NOS scale was used to evaluate the quality of the literature. Results Nineteen relevant studies,which had a total of 1 503 patients enrolled,involving 1 125 PCa,378 benign prostatic hyperplasia(BPH). The results of meta⁃analysis showed that:HIF⁃1α protein expression was higher in PCa group than that in BPH group(OR=14.30,95%CI 7.41~27.60). The results of the meta⁃analysis showed significant associations between HIF⁃1αprotein expression and higher tumor stage(C+D andⅢ+Ⅳ),high tumor grade or positive lymph node metastatic status,respectively,the combined ORs and 95%CI were as follows:OR=8.51,95%CI 4.90~14.80;OR=4.93,95%CI 2.84~8.57;OR=5.53,95%CI 3.74~8.18;OR=7.09,95%CI 3.87~12.98. There was no significant association between HIF⁃1α protein expression and age(>65 vs. ≤65),the combined OR and 95%CI were OR 1.66,95%CI 0.86~3.20. Additionally,significant correlations between HIF⁃1α protein expression and survival outcome(progression⁃free survival and metastasis⁃free survival)were also observed in PCa patients,the combined OR and 95%CI were OR 0.37,95%CI 0.17~0.81;OR 9.80,95%CI 1.50~63.86. Conclusion The present results indicate that over⁃expression of HIF⁃1αis distinctly correlated with an increased risk and poorer survival in PCa patients. HIF⁃1αmay serve as a valuable biomarker for prognosis in PCa patients.