T细胞激活抑制物免疫球蛋白可变区结构域表达与宫颈鳞状细胞癌发生发展的关系及临床意义

Correlation and clinical significance of VISTA expression and cervical squamous cell carcinoma

目的探讨T细胞激活抑制物免疫球蛋白可变区结构域(VISTA)的表达与宫颈鳞状细胞癌(CSCC)发生发展的关系,及对CSCC患者预后的影响。方法收集2014年3月至2019年4月苏州大学附属第一医院收治的116例CSCC、23例宫颈上皮内瘤变(CIN)Ⅰ级、23例CINⅡ~Ⅲ级和23例慢性宫颈炎患者的宫颈组织标本,采用免疫组化SP法检测VISTA的表达。通过随访获取CSCC患者的生存资料,采用Kaplan-Meier法进行生存分析,组间生存率比较采用Log rank检验。预后影响因素分析采用多因素Cox比例风险模型。结果CSCC组VISTA表达阳性率为32.8%(38/116),CINⅡ~Ⅲ级组阳性率为17.4%(4/23),CINⅠ级组和慢性宫颈炎组VISTA表达均为阴性。CSCC组与CINⅡ~Ⅲ级组、CINⅠ级组及慢性宫颈炎组比较,差异均有统计学意义(均P<0.01)。在116例CSCC患者中,VISTA表达与CSCC患者的国际妇产科联盟(FIGO)分期、淋巴结转移有关(均P<0.01)。VISTA阳性表达组患者平均生存时间为30.7个月,3年生存率为44.7%(17/38);而VISTA阴性表达组患者平均生存时间为49.1个月,3年生存率为87.2%(68/78)。多因素Cox回归分析显示,VISTA表达(P=0.001)和FIGO分期(P=0.047)为CSCC患者预后的独立影响因素,VISTA阳性表达患者的死亡风险是VISTA阴性表达患者的4.130倍。结论VISTA蛋白在CSCC组织中高表达,其表达水平与CSCC的发生发展密切相关。VISTA表达可作为CSCC预后的独立预测因子,为CSCC免疫检查点抑制剂治疗提供有力依据。

Objective To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region(VISTA)and the development of cervical squamous cell carcinoma(CSCC),and the impact on the prognosis of CSCC patients.Methods Cervical tissue samples from 116 CSCC,including 23 cervical intraepithelial neoplasia(CIN)grade I,23 CIN gradeⅡ-Ⅲ,and 23 chronic cervicitis patients,were collected from the First Hospital of Soochow University between March 2014 and April 2019.The expression of VISTA in each group was detected by immunohistochemistry(IHC).Survival data of CSCC patients were obtained by follow-up.The survival analysis was performed by Kaplan-Meier method,and survival differences between groups were compared by Log rank test.Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model.Results The positive rate of VISTA expression in CSCC group was 32.8%(38/116),and which of gradeⅡ-Ⅲwas 17.4%(4/23).VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups.The differences between the CSCC group and other groups were statistically significant(P<0.01).In 116 CSCC patients,VISTA expression was associated with International Federation of Gynecology and Obstetrics(FIGO)stage and lymph node metastasis(P<0.01).The mean survival time of patients in the VISTA positive expression group was 30.7 months,and the 3-year survival rate was 44.7%(17/38).However,the mean survival time of the patients in the VISTA negative expression group was 49.1 months,and the 3-year survival rate was 87.2%(68/78).The Cox regression model found that VISTA expression positivity(P=0.001)and FIGO stage(P=0.047)were prognostic factors for CSCC,and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression.Conclusions The VISTA protein is highly expressed in CSCC tissues,and its expression level is closely related to the occurrence and development of CSCC.The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.