Mcl-1表达对膀胱癌进展以及肿瘤相关巨噬细胞浸润的影响

Effects of Mcl-1 expression on bladder cancer progression and tumor-associated macrophage infiltration

目的 探讨膀胱癌Mcl-1的表达与肿瘤微环境(Tumor microenvironment, TME)中肿瘤相关巨噬细胞(Tumour-associated macrophages, TAM)的相关性,以及在膀胱癌治疗中的影响。方法 通过TCGA、GEPIA、TIMER等数据库分析膀胱癌中Mcl-1表达水平与肿瘤相关巨噬细胞、肿瘤微环境免疫细胞和基质细胞浸润的相关性。免疫组织化学检测膀胱癌组织及癌旁组织中M1/M2型巨噬细胞、Mcl-1的表达。结果 膀胱癌组织中Mcl-1表达与膀胱肿瘤微环境免疫评分(Immune Score)和基质评分(Stromal Score)正相关(P<0.001)、M1/M2型肿瘤相关巨噬细胞及其标志物(M1:CD86;M2:CD163)正相关(P<0.001)、患者的总生存期呈负相关(P<0.05)。免疫组织化学结果显示,与膀胱癌旁组织相比,CD86、CD163、Mcl-1在膀胱癌组织中显著高表达(P<0.001);Mcl-1表达水平与膀胱癌病理分级相关(P<0.05)。结论 膀胱癌中Mcl-1的表达与肿瘤相关巨噬细胞极化密切相关,可调控Mcl-1影响M1/M2型巨噬细胞,辅助BCG膀胱灌注免疫治疗。

Objective To explore the correlation between the expression of Mcl-1 in bladder cancer and the tumor-associated macrophages(TAM) in the tumor microenvironment(TME), as well as its influence in the treatment of bladder cancer.Methods The correlation between the expression level of Mcl-1 in bladder cancer and tumor-associated macrophages, tumor microenvironment immune cells and stromal cell infiltration was analyzed by TCGA, GEPIA, TIMER and other databases. Immunohistochemistry was used to detect the expression of M1/M2 macrophages and Mcl-1 in bladder cancer tissues and adjacent tissues.Results Mcl-1 expression in bladder cancer tissue was positively correlated with bladder tumor microenvironment immune score(Immune Score) and stromal score(P<0.001), M1/M2 tumor-associated macrophages and their markers(M1: CD86;M2: CD163) were positively correlated(P<0.001), and the overall survival of patients was negatively correlated(P<0.05). The results of immunohistochemistry showed that compared with bladder adjacent tissues, CD86, CD163 and Mcl-1 were significantly higher in bladder cancer tissue(P<0.001);the expression level of Mcl-1 was correlated with the pathological grade of bladder cancer(P<0.05). Conclusion The expression of Mcl-1 in bladder cancer is closely related to the polarization of tumor-associated macrophages, and it can regulate Mcl-1 to affect M1/M2 macrophages and assist BCG intravesical immunotherapy.