Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis

PurposeThis study was to quantitatively summarize published data for evaluating the clinical and prognostic significance of four proteins involved in hypoxia-inducible factor-1 (HIF-1α) regulation of the metastasis cascade.MethodsSearches were performed using the MEDLINE, EMBASE, Cochrane Library, and Chinese Biomedicine databases without any language restrictions. Studies were pooled and either the summary risk ratio (RR) or odds ratio (OR) was calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias was also performed.ResultsSeventeen studies evaluated HIF-1α, 20 studies evaluated phosphatase and tensin homolog (PTEN), 20 studies evaluated Survivin, and 16 studies evaluated CD44v6. Our results showed that increased HIF-1α expression was linked to a poor 5-year overall survival (RR = 1.508; 95% confidence interval (CI) 1.318–1.725; P2 for the main stratified meta-analyses of clinical factors.ConclusionsOur findings indicate that HIF-1α/PTEN/CD44v6/Survivin, as measured by immunohistochemistry, can be used to predict the prognosis and potential for invasion and metastasis in Asian patients with gastric cancer. The development of strategies against this subset of proteins could lead to new therapeutic approaches.

目的：本研究旨在定量汇总已发表数据，以评估参与缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）调控肿瘤转移级联反应的四种蛋白质的临床与预后意义。方法：本研究检索了MEDLINE、EMBASE、Cochrane图书馆及中国生物医学文献数据库，未设置语言限制。对纳入研究进行合并分析，计算汇总风险比（summary risk ratio，RR）或比值比（odds ratio，OR）。通过亚组分析与敏感性分析探寻异质性的潜在来源，并开展发表偏倚检测。结果：共纳入17项针对HIF-1α的研究、20项针对磷酸酶与张力蛋白同源物（phosphatase and tensin homolog，PTEN）的研究、20项针对生存素（Survivin）的研究及16项针对CD44v6的研究。本研究结果显示，HIF-1α表达上调与较差的5年总生存期相关（RR=1.508；95%置信区间（CI）1.318~1.725；原文此处标注为P2）。按临床因素分层的主要分层Meta分析存在显著异质性。结论：本研究结果表明，经免疫组织化学（immunohistochemistry）检测的HIF-1α、PTEN、Survivin及CD44v6，可用于预测亚洲胃癌患者的预后及侵袭转移潜能。针对该类蛋白的干预策略研发，有望为胃癌治疗带来全新的治疗思路与方法。