程序性细胞死亡配体1状态与乳腺癌放疗敏感性的关系

The relationship between PD-L1 status and radiosensitivity of breast cancer

目的程序性细胞死亡配体1(PD?L1)在恶性肿瘤的治疗中起重要作用。文中探讨PD?L1状态与乳腺癌放疗及临床预后之间的关系。方法采用癌症基因组图谱(TCGA)数据库分析浸润性乳腺癌中PD?L1表达状态、放疗和预后关系。TCGA库中1007例乳腺癌患者被纳入统计分析。根据总样本CD274mRNA表达中值,纳入患者被划分为PD?L1高状态组(503例)和PD?L1低状态组(504例)。对高、低状态组患者是否放疗分别进行生存分析。结果单因素分析显示,PD?L1高状态患者相比低状态患者生存率得到改善,差异有统计学意义(P=0.047)。PD?L1高状态组,放疗与非放疗患者之间总生存率差异无统计学意义(P=0.352);多因素分析校正后差异仍无统计学意义(P=0.242)。PD?L1低状态组接受放疗较未放疗患者的总生存率提高(HR=0.550,95%CI 0.335～0.904, P=0.017);多因素分析校正后差异仍有统计学意义(HR=0.415, 95%CI 0.194～0.872,P=0.025)。PD?L1状态与ER状态(χ~2=18.44,P<0.001)、HER2状态(χ~2=7.943,P=0.047)和分子分型(χ~2=14.52,P=0.006)有关,而状态无关。结论 PD?L1状态与乳腺癌的放疗敏感性存在关联性。低状态PD?L1患者术后接受放疗总生存率改善,推测PD?L1可能是乳腺癌放疗敏感性基因。

Objective Programmed cell death ligand 1(PD-L1)plays an important role in the treatment of malignant tumors.The study explores the relationship between PD-L1 status and breast cancer radiotherapy and clinical prognosis.Methods Using the Cancer Genome Atlas(TCGA)database analyze the relationshipof PD-L1 expression,radiotherapy and prognosis in breast cancer.1007 patients were included in the statistical analysis.Based on the median value of CD274 mRNA expression levels in the database,the total sample was divided into a PD-L1-high state group(503 cases)and a PD-L1-low state group(504 cases).Survival analysis was carried out for patients in the high and low state group with and without radiotherapyrespectively.Results The univariate analy-sis showed that the overall survival rate was improved in patients with PD-L1high status compared with patients with PD-L1-low status.The difference was statistically significan(t P=0.047).InPD-L1-high status group,univariate analysis and multivariate analysis showed no significant difference in the overall survival rate between patients with radiotherapy and without radiotherapy,and the P values were 0.352 and 0.242 respectively.However,theoverallsurvivalrateofra-diotherapy patients with PD-L1-low status group was significantly im-proved(HR0.550,95%CI:0.335-0.904,P=0.017),and there was still statistical significance after multivariate factors adjustment(HR0.415,95%CI:0.194-0.872,P=0.025).Chi-square analysis showed that PD-L1 status was associated with ER status(L=18.44,P<0.001),HER2 status(x^2=7.943,P=0.047)and molecular typing(x^2=14.52,P=0.006),but not with age,histological type,surgical treatment,postoperative tissue margin status and PR status.Conclusion The PD-L1 status was associated with the radiosensitivity of breast cancer.The overall survival rate of postoperative radiotherapy in patients with PD-L1-low expressionwas significantly improved.lt is speculated that PD-L1 may be a radiosensitivity gene for breast cancer.