Combined prognostic value of the cancer stem cell markers CD47 and CD133 in esophageal squamous cell carcinoma
Combined prognostic value of the cancer stem cell markers CD47 and CD133 in esophageal squamous cell carcinoma
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癌症干细胞标志物CD47和CD133在食管鳞癌中的联合预后价值
DOI：
10.1002/cam4.1894
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发表时间：
2019-03-01
期刊：
影响因子：
4
通讯作者：
Zheng, Min
中科院分区：
文献类型：
--
作者：
Wang, Jian-Hua;Huang, Shu-Ting;Zheng, Min
背景 基于抑制癌症干细胞 (CSC) 关键信号的治疗正在走上有希望的道路。最近的研究表明，使用更广泛的基于免疫的治疗方法（例如抗 CD47 治疗）来靶向 CSC，可能是消除这些顽固细胞的更有效策略。我们的目的是探讨CD47/CD133的预后作用以及CD47在食管鳞状细胞癌（ESCC）中的潜在治疗意义。方法采用免疫组化方法检测26对肿瘤组织及癌旁非肿瘤组织和136例食管鳞癌组织中CD47和CD133的特征。建立 Kaplan-Meier 分析和 Cox 比例风险模型来估计 CD47 和 CD133 表达及其组合干性指数的预后值。进行球体形成测定以探索 CD47 抑制对原代人 ESCC CSC 的影响。结果结果得出结论，与邻近的非肿瘤组织相比，肿瘤组织中的CD47和CD133表达增加。在 136 名 ESCC 患者中发现 CD47/CD133 表达与分化呈正相关。生存分析表明，CD47 或 CD133 高表达的患者总体生存率和无进展生存期 (PFS) 较差。高 CD47 和 CD133 表达的组合是 OS（HR = 1.940，95% CI = 1.399-2.690，P < 0.0001）和无进展生存期（HR = 1.883，95% CI = 1.384-2.562，P < 0.0001）的可靠独立预后因素。值得注意的是，CD47+ CD133+ ESCC 细胞被观察到具有 CSC 的特征，抗 CD47 治疗确实消除了 CSC 库。结论 CD47和CD133表达确定的干性指数是一个有前景的预后预测因子，CD47是ESCC患者CSC的潜在治疗靶点。
Background Treatments based on the inhibition of pivotal signals of cancer stem cells (CSCs) are on a promising track. Recent studies have shown that targeting CSCs with broader immune-based therapeutic methods, for example, the anti-CD47 treatment, may serve as a more potent strategy for eliminating these intractable cells. We aimed to explore the prognostic effects of CD47/CD133 and the potential therapeutic significance of CD47 in esophageal squamous cell carcinoma (ESCC). Methods Immunohistochemistry was employed to identify the characteristics of CD47 and CD133 in 26 pairs of tumor tissues and adjacent non-tumor tissues and 136 ESCC tissues. Kaplan-Meier analysis and Cox proportional hazards models were built for estimating the prognostic values of CD47 and CD133 expression and their combined stemness index. Sphere formation assays were undertaken to explore the effects of CD47 inhibition on primary human ESCC CSCs. Results Results conclude that CD47 and CD133 expression is increased in tumor tissues as compared to adjacent non-tumor tissues. A positive correlation between CD47/CD133 expression and differentiation was found in 136 ESCC patients. Survival analysis indicated that patients with high CD47 or CD133 expression exhibited poor overall survival and progression-free survival (PFS). The combination of high CD47 and CD133 expression was a reliable independent prognostic factor for both OS (HR = 1.940, 95% CI = 1.399-2.690, P < 0.0001) and progression-free survival (HR = 1.883, 95% CI = 1.384-2.562, P < 0.0001). Notably, CD47+ CD133+ ESCC cells were observed to possess the characteristics of CSCs, and anti-CD47 treatment veritably eliminated the CSCs pool. Conclusions The stemness index determined by the expression of CD47 and CD133 is a promising prognostic predictor, and CD47 is a potential therapeutic target for CSCs in ESCC patients.