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

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 tissue39.7%(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 (χ²=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.