关键词: 生长停滞特异基因1, 乳腺癌, 免疫治疗, 药物敏感性

Abstract: Objective The aim of this study was to explore the relationship between growth arrest specific gene 1(GAS1), immunotherapy and drug sensitivity in breast cancer patients. Methods The expression of GAS1 in breast tissues and its relationship with clinicopathological features were analyzed using TCGA database data. The relationship between GAS1 and gene set was explored by GSEA enrichment analysis. The CIBERSORT method was used to analyze the proportion of 22 types of immune cells and explore the relationship between GAS1 and immune infiltrating cells. The TCIA database was used to evaluate the relationship between GAS1 expression and the CTLA4 and PD1 immunophenotypic scores. The GDSC database was used to explore the relationship between GAS1 and different drug sensitivities. The data of 96 cases of breast cancer patients and 33 cases of adjacent tissues from January 2016 to December 2017 in the department of Breast Surgery, Cancer Hospital of Harbin Medical University were used for GAS1 immunohistochemical staining verification. Results The results of TCGA database showed that the expression of GAS1 in breast cancer tissues was significantly lower than that in breast adjacent tissues(P＜0.001), and the level of GAS1 was correlated with age(P=0.040). Multiple pathways, including cell adhesion molecules, were mainly enriched in the high expression group of GAS1. There were significant differences in CD8 T cells, follicular helper T cells and macrophage M1 between the high and low expression groups of GAS1(P＜0.05). The ips_ctla4_neg_pd1_pos and ips_ctla4_pos_pd1_pos scores in the high expression group of GAS1 were higher than those of the low expression group of GAS1, and the difference was statistically significant(P＜0.05). The IC₅₀ values of docetaxel, epirubicin, cisplatin, fluvestrant, paclitaxel, palbociclib, and olaparib in the high expression group of GAS1 were lower than those in the low expression group, and the difference was statistically significant(P＜0.05). In clinical samples, the proportion of high GAS1 expression in cancer tissue of breast cancer patients was significantly lower than that in adjacent tissues(P＜0.001). The expression of GAS1 was related to whether the molecular typing was triple negative, histological grading, and CK5/6 status(P＜0.05). Conclusion Breast cancer patients with high GAS1 expression are more sensitive to the immunotherapeutic drug PD1 and some common chemotherapy drugs, and GAS1 can be used to predict the sensitivity of breast cancer patients to these drugs.

Key words: Growth arrest specific gene 1, Breast cancer, Immunotherapy, Drug sensitivity