程序性死亡受体配体1与肿瘤相关成纤维细胞在乳腺癌组织中的表达及临床意义

Expression of programmed death⁃ligand 1 and cancer⁃associated fibroblasts in breast cancer tissues and its clinical significance

目的探讨肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)与程序性死亡受体配体1(programmed deathligand 1,PD-L1)在乳腺浸润性导管癌中的表达及临床价值。方法收集2019年1月至2021年6月于南通大学第二附属医院行乳腺癌改良根治术的手术标本121例,均为乳腺浸润性导管癌。采用免疫组织化学染色检测乳腺癌组织中CAFs、PD-L1的表达,并分析CAFs、PD-L1与临床病理特征的关系,采用Spearman相关分析CAFs表达与PD-L1表达的相关性,单因素和多因素Cox回归分析可能影响无进展生存期(progression-free survival,PFS)的因素;采用Kaplan-Meier法绘制生存曲线,Log-rank检验比较生存差异。结果CAFs在乳腺癌组织中呈高表达,且与肿瘤大小、淋巴结转移及TNM分期显著相关(均P<0.01);PD-L1在乳腺癌组织中呈高表达,且与淋巴结转移、TNM分期及雌激素受体(estrogen receptor,ER)表达显著相关(均P<0.01)。乳腺癌组织中CAFs阳性表达与PD-L1阳性表达呈正相关(r=0.265,P=0.011)。单因素Cox回归分析显示,乳腺癌组织学分级、淋巴结转移、TNM分期、ER阴性表达、PD-L1表达与其预后相关(均P<0.05),多因素Cox回归分析显示PD-L1阳性表达是PFS较差的独立危险因素(P<0.05)。生存分析显示,PD-L1阴性表达组和阳性表达组1年PFS率(100.00%vs 84.09%;χ^(2)=11.115,P=0.001)和3年PFS率(95.92%vs 79.55%;χ^(2)=6.312,P=0.012)比较差异均有统计学意义。结论CAFs和PD-L1在乳腺癌组织中呈高表达,PD-L1表达与预后不良相关,CAFs与PD-L1在促进乳腺癌的恶性进展中可能存在相互作用,有望成为乳腺癌免疫治疗的新靶点。

Objective To investigate the expression and clinical value of cancer⁃associated fibroblasts(CAFs)and programmed death⁃ligand 1(PD⁃L1)in breast invasive ductal carcinoma.Methods A total of 121 surgical specimens of breast invasive ductal carci⁃noma were collected in the Second Affiliated Hospital of Nantong University who underwent modified radical mastectomy,from January 2019 to June 2021.The expression of CAFs and PD⁃L1 in breast cancer tissues were detected by using immunohistochemical staining,and the correlation of CAFs and PD⁃L1 with clinicopathological features was analyzed.Spearman correlation analysis was used to analyze the correlation between the expression of CAFs and PD⁃L1.The factors affecting the progression⁃free survival(PFS)were analyzed based on univariate and multivariate Cox analyses.Kaplan⁃Meier method was used to draw the survival curve and Log⁃rank test was used to compare the survival difference.Results CAFs was highly expressed in breast cancer tissues and were significantly correlated with tumor size,lymph node metastasis and TNM stage(all P<0.01).PD⁃L1 was highly expressed in breast cancer tissues,and was significantly correlated with lymph node metastasis,TNM stage and estrogen receptor(ER)expression(all P<0.01).The positive expression of CAFs was positively correlated with that of PD⁃L1 in breast cancer tissues(r=0.265,P=0.011).Univariate Cox analysis showed that histological grade,lymph node metastasis,TNM stage,ER positive expression and PD⁃L1 expression were all correlated with the prognosis of breast cancer(all P<0.05).Multivariate Cox analysis showed that positive PD⁃L1 expression was an independent risk factor for poor PFS(P<0.05).Survival analysis showed that there were statistically significant differences in 1⁃year PFS rate(100.00%vs 84.09%;χ^(2)=11.115,P=0.001)and 3⁃year PFS rate(95.92%vs 79.55%;χ^(2)=6.312,P=0.012)between the PD⁃L1 negative expression group and the PD⁃L1 positive expression group.Conclusions CAFs and PD⁃L1 are highly expressed in breast cancer tissues,and PD⁃L1 is associated with poor prognosis.There may exist interplay between CAFs and PD⁃L1 in promoting the malignant progression of breast cancer,which is expected to become a new target for the immunotherapy of breast cancer.