免疫检查点蛋白VISTA在乳腺癌中的表达及对预后的影响

Expression of immune checkpoint protein VISTA in breast cancer and its effect on the prognosis of breast cancer patients

目的探讨VISTA在乳腺癌的表达情况及与乳腺癌临床因素的相关性;评估VISTA在乳腺癌中的预后价值。方法采用免疫组织化学方法分析140例乳腺癌肿瘤组织的病理切片的微阵列,分析肿瘤细胞(TC)VISTA表达、免疫细胞(IC)VISTA表达和VISTA的综合阳性评分(CPS)与临床变量的关系,以及与乳腺癌生存预后的相关性;再从癌基因数据库TCGA提取乳腺癌VISTA mRNA表达量数据,验证其与生存预后的相关性。结果乳腺癌组织中检测到VISTA表达率为35.0%,其中VISTA在TC中的表达率为11.4%,在IC中的表达率为30.0%。乳腺癌VISTA蛋白的CPS与雌激素受体(ER)阴性、孕激素受体(PR)阴性、三阴性者存在显著相关性(P=0.005、0.010、0.001);TC VISTA阳性表达与PR阴性存在显著相关性(P=0.016);IC VISTA阳性表达与人类表皮生长因子受体2(HER2)阳性存在显著相关性(P=0.013)。IC VISTA阳性表达者与阴性者相比,生存率显著提高(90.2%vs.73.4%,P=0.038);而VISTA的CPS(79.3%vs.75.3%,P=0.601)和TC的VISTA表达(73.1%vs.79.2%,P=0.478)不具有此现象;VISTA mRNA高表达与低表达者间的总生存的预后指标无显著性差异(P=0.246)。IC VISTA阳性表达是乳腺癌总生存的独立良好预后指标(P=0.017),也是HER2阴性乳腺癌的良好预后指标(P=0.046)。结论乳腺癌组织中VISTA在IC中的表达率高于TC;VISTA阳性表达与HER2阳性和PR阴性相关;IC VISTA阳性表达是乳腺癌良好总生存的预后指标,也是HER2阴性乳腺癌的良好预后指标。

Objective To explore the expression of V-type immunoglobulin domain-containing suppressor of T cell activation(VISTA)in breast cancer and its correlation with clinical factors,and evaluate the prognostic value of VISTA in breast cancer.Methods Immunohistochemical method was used to analyze the microarray of pathological sections of 140 cases of breast cancer tumor tissues.The expressions of VISAT in tumor cells(TC)and immune cells(IC),and the combined positive score(CPS)were analyzed,and the relationship with clinical variables and the correlation with survival and prognosis of breast cancer were also investigated.Then the VISTA mRNA expression data of breast cancer was extracted from the oncogene database The Cancer Genome Atlas(TCGA)to verify its correlation with survivial and progosis.Results The expression rate of VISTA in breast cancer tissues was 35.0%,11.4%in TC and 30.0%in IC.The CPS of VISTA was observed significantly higher in ER-negative,PR-negative or three-negative sample(P=0.005,0.010 and 0.001,respectively).VISTA-positive TC were significantly correlate with PR-negative sample(P=0.016).VISTA-positive IC was significantly correlated with HER2-positive sample(P=0.013).The survival rate of VISTA positive expression in IC was significantly higher than that of negative expression(90.2%vs.73.4%,P=0.038).However,the CPS of VISTA(79.3%vs.75.3%,P=0.601)and the VISTA expression of tumor cells(73.1%vs.79.2%,P=0.478)did not show this phenomenon.There was no significant difference in overall survival between the patients with high and low VISTA mRNA expression(P=0.246).Positive expression of VISTA in IC was an independent and good prognostic indicator of overall survival of breast cancer(P=0.017),and it was also a good prognostic indicator of human epidermal growth factor receptor 2-negative(HER2)breast cancer(P=0.046).Conclusion The expression rate of VISTA in breast cancer tissues is higher than that in TC.VISTA positive expression is related to HER2-positive and PR-negative tumors.The positive expression of VISTA in IC is a good prognostic indicator for the overall survival of breast cancer,and it is also a good prognostic indicator for HER2-negative breast cancer.