乳腺癌组织中STING和CD68的表达及其临床意义

Expression and clinical significance of STING and CD68 in breast cancer tissues

目的:探讨干扰素基因刺激因子(STING)和CD68在乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学SP法检测83例乳腺癌病人癌组织及其癌旁组织中STING和CD68的表达情况,分析上述两种蛋白的表达与乳腺癌病人临床病理参数、临床预后之间的关系,并结合TGCA数据库进行生物信息分析两种蛋白表达情况的相关性及其代表的cGAS-STING信号通路于肿瘤相关巨噬细胞的相关性。结果:STING蛋白在乳腺癌组织中的阳性表达率为24.1%(20/83),低于癌旁组织中的39.7%(33/83)(P<0.05),其表达情况与病人的HER-2阳性率、分子分型相关(P<0.05)。CD68蛋白在乳腺癌组织中的阳性表达率为69.8%(58/83),高于癌旁组织中的39.7%(33/83)(P<0.01),其表达情况与病人的分子分型、TNM分期、淋巴结转移相关(P<0.05)。STING蛋白表达水平与病人中位生存期相关,高表达组中位OS为42个月(95%CI:34.263~49.458),STING低表达组中位OS为19个月(95%CI:17.614~24.683),差异有统计学意义(χ^(2)=6.25,P<0.05)。结合生物信息分析,STING蛋白表达水平与CD68表达水平呈正相关关系(Kappa=0.241,r=0.636,P<0.01)。乳腺癌中STING表达水平与包括巨噬细胞在内的各种免疫细胞浸润密切相关,并且与巨噬细胞M1/M2极化标志物表达水平呈正相关关系。结论:乳腺癌病人癌组织中STING蛋白表达降低,CD68蛋白表达升高,两者可能共同参与乳腺癌的进展,从cGAS-STING信号通路活化可能有助于TAMs浸润及极化,STING激动剂有望成为TAMs调控和增强免疫治疗响应性的有效手段。

Objective:To investigate the expression and clinical significance of stimulator of interferon gene(STING)and CD68 in breast cancer tissues.Methods:Immunohistochemical SP method was used to detect the expression levels of STING and CD68 in cancer tissues and adjacent tissues of 83 breast cancer patients.The relationship between the expression of two proteins and clinicopathological parameters,clinical prognosis of breast cancer patients were analyzed.The correlations of the expression between the two proteins,and between cGAS-STING signaling pathway and tumor-associated macrophages were analyzed using the biological information analysis of TGCA database.Results:The positive expression rate of STING protein in breast cancer tissues was 24.1%(20/83),which was lower than that in adjacent tissue[39.7%(33/83),P<0.05],and correlated with the HER-2 positive rate and molecular typing of patients(P<0.05).The positive expression rate of CD68 in breast cancer tissues was 69.8%(58/83),which was higher than that in adjacent tissue[39.7%(33/83),P<0.05],and correlated with the TNM stage,lymph node metastasis and molecular typing of patients(P<0.05).The expression level of STING protein was correlated with the median survival of patients.The median OS in the high-expression group was 42 months(95%CI:34.263-49.458),the median OS in the low-expression group was 19 months(95%CI:17.614-24.683),and the difference of which was statistically significant(χ^(2)=6.25,P<0.05).The results of biological information analysis showed that the expression level of STING protein was positively correlated with the CD68 expression level(Kappa=0.241,r=0.636,P<0.01).The expression level of STING in breast cancer was closely related to the infiltration of various immune cells,including macrophages,and positively correlated with the expression level of M1/M2 polarization markers in macrophages.Conclusions:The expression of STING protein decreases,and the CD68 protein increases in the cancer tissues of breast cancer patients,both of which may be involved in the progression of breast cancer.Activation of the cGAS-STING signaling pathway may contribute to the infiltration and polarization of TAMs,and STING agonists are expected to become an effective means to regulate TAMs and enhance the response to immunotherapy.