骨肉瘤中survivin阳性循环肿瘤细胞水平与免疫逃逸和预后的关系。
Association of survivin positive circulating tumor cell levels with immune escape and prognosis of osteosarcoma.
发表日期:2023 Aug 01
作者:
Jili Lu, Haijun Tang, Lin Chen, Nenggan Huang, Guofang Hu, Chong Li, Kai Luo, Feicui Li, Shangyu Liu, Shijie Liao, Wenyu Feng, Xinli Zhan, Jifeng Miao, Yun Liu
来源:
Immunity & Ageing
摘要:
骨肉瘤(OS)循环肿瘤细胞(CTCs)中的survivin蛋白(由BIRC5编码)的功能尚未被研究。本研究的目标是确定CTCs的survivin蛋白表达是否与循环免疫细胞浸润和OS的疾病预后相关。收集了20名OS患者的血液样本。应用CanPatrol™ CTC富集技术结合原位杂交(ISH)来富集和检测CTCs和survivin蛋白。将生物信息学分析与常规血液检测数据相结合,验证survivin与循环系统的免疫细胞浸润之间的关联。使用Kaplan-Meier生存曲线,单变量和多变量Cox回归分析来筛选独立的预后因素。生物信息学分析显示,BIRC5与淋巴细胞(包括T细胞、NK细胞和B细胞)呈强烈负相关,表明BIRC5通过降低循环系统的免疫细胞浸润,在免疫逃逸中发挥关键作用。同时,survivin+ CTCs的数量与淋巴细胞计数显著负相关(R = -0.56,p = 0.011),与生物信息学分析一致。Kaplan-Meier曲线显示,高survivin+ CTCs组的总生存率显著低于低组(88.9%vs 36.4%,p = 0.04)。多变量Cox回归分析显示,survivin+ CTCs是独立的预后因素(p = 0.019)。这些发现表明,survivin蛋白在CTCs的免疫逃逸中起关键作用,并且survivin+ CTCs的存在可能是OS患者的一个有前景的预后因素。
©2023. 作者,独家授权给Springer-Verlag GmbH德国,Springer Nature的一部分。
Function of survivin protein (encoded by BIRC5) in circulating tumor cells (CTCs) of osteosarcoma (OS) has not been investigated. The goal of this study is to determine whether the expression of survivin protein of CTCs is associated with circulating immune cell infiltration and disease prognosis of OS.Blood samples of 20 patients with OS were collected. CanPatrol™ CTC enrichment technology combined with in situ hybridization (ISH) was applied to enrich and test CTCs and survivin protein. Bioinformation analysis combined with data of routine blood test was used to verify the association between survivin and immune cell infiltration in circulatory system. To screen independent prognostic factors, Kaplan-Meier survival curve, univariate and multivariable Cox regression analyses were performed.Bioinformatics analysis showed that BIRC5 was strongly negatively related to lymphocyte, including T cell, NK cell and B cell, which released that BIRC5 played a key role in immune escape via reducing immune cell infiltration in circulatory system. Meanwhile, the number of survivin+ CTCs was significantly negatively connection with lymphocyte count (R = -0.56, p = 0.011), which was consistent with bioinformatics analysis. Kaplan-Meier curve showed that the overall survival rate in high survivin+ CTCs group was significantly lower than low group (88.9% vs 36.4%, p = 0.04). Multivariable Cox regression analyses showed that survivin+ CTCs were an independent prognostic factor (p = 0.019).These findings suggested that survivin protein played a key role in immune escape of CTCs and the presence of survivin+ CTCs might be a promising prognostic factor in OS patients.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.