Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, The University of Toronto, Toronto, ON, Canada.
Experimental Therapeutics Unit, Medical Oncology Department, Health Research Institute of the Hospital Clínico San Carlos, Madrid, Spain.
Mol Diagn Ther. 2020 Apr;24(2):143-151. doi: 10.1007/s40291-020-00450-1.
Integrins are a family of adhesion receptor proteins that provide signaling from the extracellular matrix to the cytoplasm. They have been associated with cancer by promoting migration, invasion, metastasis, and survival. ανβ6 integrin is upregulated in several tumors. Here, we evaluate the prognostic impact of ανβ6 integrin protein expression in solid tumors.
A systematic search of electronic databases identified publications exploring the effect of ανβ6 integrin on overall survival (OS). Hazard ratios (HRs) were pooled in a meta-analysis using generic inverse variance and random effects modeling. Subgroup analyses were conducted based on tumor site, tumor stage, antibody used for immunohistochemistry (IHC) and method for extraction of the HR. A meta-regression explored the influence of clinical variables on the magnitude of effect of ανβ6 integrins on OS.
Seventeen studies comprising 5795 patients met the inclusion criteria. High ανβ6 integrin expression in tumors was associated with worse OS (HR 1.65, 95% confidence interval [CI] 1.32-2.06; Cochran's Q p < 0.001, I = 81%). Adverse outcomes were similar in all tumor sites (subgroup difference p = 0.10), with the strongest association between ανβ6 integrins and OS in gastric cancer (HR 2.20, 95% CI 1.71-2.83) and the lowest in head and neck cancer (HR 1.21, 95% CI 0.79-1.83). There was no significant difference between early-stage and metastatic cancer, type of IHC antibodies, and analysis methods.
High expression of ανβ6 integrins is associated with adverse survival outcome in several tumors. Prospective studies evaluating the prognostic impact of ανβ6 integrin and its role as a therapeutic target are warranted.
整合素是一组细胞外基质与细胞质之间信号传递的黏附受体蛋白。它们通过促进迁移、侵袭、转移和存活与癌症有关。在几种肿瘤中，αvβ6 整合素表达上调。在这里，我们评估固体肿瘤中αvβ6 整合素蛋白表达的预后影响。
系统地检索电子数据库，确定了探讨αvβ6 整合素对总生存（OS）影响的出版物。使用通用逆方差和随机效应模型对荟萃分析中进行了风险比（HRs）的汇总。根据肿瘤部位、肿瘤分期、用于免疫组织化学（IHC）的抗体以及提取 HR 的方法进行了亚组分析。Meta 回归探索了临床变量对αvβ6 整合素对 OS 影响程度的影响。
有 17 项研究共纳入 5795 例患者符合纳入标准。肿瘤中高表达αvβ6 整合素与 OS 较差相关（HR 1.65，95%置信区间 [CI] 1.32-2.06；Cochran's Q p<0.001，I=81%）。所有肿瘤部位的不良结局均相似（亚组差异 p=0.10），αvβ6 整合素与 OS 之间的最强相关性见于胃癌（HR 2.20，95%CI 1.71-2.83），最低见于头颈部癌症（HR 1.21，95%CI 0.79-1.83）。早期和转移性癌症、IHC 抗体类型和分析方法之间无显著差异。
αvβ6 整合素的高表达与几种肿瘤的不良生存结局相关。需要进行前瞻性研究评估αvβ6 整合素的预后影响及其作为治疗靶点的作用。
