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双阴性T细胞和T淋巴细胞亚群在乳腺癌中表达特征及其诊断价值

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目的 探讨双阴性T(DNT)细胞及T淋巴细胞亚群在乳腺癌中的表达情况以及与乳腺癌临床病理特征的关系,并联合肿瘤标志物分析对乳腺癌筛查的诊断价值.方法 采用病例对照研究方法,回顾性选取2021-09-30-2023-04-18中国人民解放军联勤保障部队第九六○医院乳腺癌患者82例(乳腺癌组)、乳腺良性肿瘤患者88例(乳腺良性肿瘤组)及健康体检者81名(健康组).采用流式细胞术检测分析3组外周血DNT细胞及T淋巴细胞亚群的表达情况,并探讨DNT细胞及其亚群与乳腺癌的临床病理关系.采用二元logistic回归分析乳腺癌发生的影响因素,受试者工作特征(ROC)曲线评估DNT细胞及肿瘤标志物癌胚抗原(CEA)、糖类抗原125(CA125)和糖类抗原15-3(CA15-3)单独或联合检测在乳腺癌中的诊断效能.结果 乳腺癌组CD4+T细胞百分比、CD4+/CD8+比值及DNT细胞百分比分别为33.74%、1.35和7.84%,均高于健康组的26.75%、1.02和3.82%,并且乳腺癌组和乳腺良性肿瘤组的DNT细胞百分比分别为7.84%和4.34%,而乳腺良性肿瘤组CD4+T细胞百分比和CD4+/CD8+比值分别为34.28%和1.32,均高于健康组的26.75%和1.02,差异均有统计学意义,P<0.001.CD3+T细胞百分比和CD4+T细胞百分比在乳腺癌病理分型中差异均有统计学意义,P值分别为0.019和0.002.与乳腺癌淋巴无转移者相比,转移组CD3+T细胞百分比、CD4+T细胞百分比及DNT细胞百分比均降低,差异有统计学意义,P值分别为0.009、0.047和0.005.与乳腺癌早期(Ⅰ+Ⅱ期)者相比,晚期(Ⅲ+Ⅳ期)者CD3+T细胞百分比、CD4+T细胞百分比及DNT细胞百分比均降低,差异有统计学意义,P值分别为<0.001、0.003和0.027.增殖细胞核抗原Ki-67高表达者CD4+T细胞百分比低于低表达者,差异有统计学意义,P=0.041.乳腺癌分子分型中CD3+T细胞百分比、DNT细胞百分比差异均有统计学意义,P值分别为0.046和0.016.二元logistic回归分析提示,CD4+T细胞百分比、DNT细胞百分比、CEA、CA125和CA15-3是乳腺癌发生的影响因素,差异均有统计学意义,P值分别为0.002、<0.001、0.038、0.004和0.013.ROC曲线显示,用DNT 细胞百分比、CEA、CA125、CA15-3、CEA+CA125+CA15-3 和 DNT+CEA+CA125+CA15-3 评估健康组和乳腺癌组时曲线下面积分别为0.810、0.702、0.714、0.727、0.812和0.897,评估乳腺肿瘤良恶性时曲线下面积分别为0.739、0.684、0.665、0.700、0.774和0.838.结论 外周血T淋巴细胞亚群在乳腺良恶性肿瘤中存在显著差异,其中乳腺癌患者DNT细胞显著增高.DNT细胞及T淋巴细胞亚群与乳腺癌临床病理特征存在统计学意义的关联,并且DNT细胞和CEA、CA125、CA15-3联合检测能够提高乳腺癌的诊断效能.
Expression characteristics and diagnostic value of double-negative T cells and T lymphocyte subsets in breast cancer
Objective To investigate the expression of double-negative T(DNT)cells and T lymphocyte subsets in breast cancer and their relationship with clinicopathological features of breast cancer,and the diagnostic value of breast cancer screening combined with tumor marker analysis.Methods A case-control study was used to retrospectively select 82 pa-tients with breast cancer(breast cancer group),88 patients with benign breast tumor(benign breast tumor group)and 81 healthy physical examination subjects(healthy group)from 960th Hospital of the PLA Joint Logistics Support Force from September 30,2021 to April 18,2023.The expression of DNT cells and T lymphocyte subsets in peripheral blood of the three groups was analyzed by flow cytometry,and the clinicopathological relationship between DNT cells and their subsets and patients with breast cancer was discussed.The influencing factors of breast cancer occurrence were analyzed by binary logistic regression.The diagnostic efficacy of DNT cell and tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125)and carbohydrate antigen 15-3(CA15-3)alone and in combination in breast cancer was evaluated u-sing receiver operating characteristic(ROC)curves.Results In breast cancer group,CD4+T cell percentage,CD4+/CD8+ratio and DNT cell percentage were 33.74%,1.35 and 7.84%,respectively,higher than 26.75%,1.02 and 3.82%in the healthy group.DNT cell percentage of 7.84%in the breast cancer group was higher than that of 4.34%in the benign tumor group.The percentage of CD4+T cells and the ratio of CD4+/CD8+in the benign tumor group were 34.28%and 1.32,higher than those in the healthy group(26.75%and 1.02),respectively.The differences were statis-tically significant(P<0.001).The percentage of CD3+T cells and the percentage of CD4+T cells were significantly dif-ferent in the pathological classification of breast cancer(P=0.019 and P=0.002).The percentages of CD3+T cells,CD4+T cells and DNT cells in the metastatic group were lower than those in the group without lymphatic metastasis,and the differences were statistically significant(P=0.009,P=0.047 and P=0.005).Compared with the early stage of breast cancer(stage Ⅰ+Ⅱ),the percentage of CD3+T cells,CD4+T cells and DNT cells in the advanced group(stageⅢ+Ⅳ)were decreased,and the differences were statistically significant(P<0.001,P=0.003 and P=0.027).The percentage of CD4+T cells in high expression group was lower than that in low expression group,and the difference was statistically significant(P=0.041).There were significant differences in the percentage of CD3+T cells and the percent-age of DNT cells in the molecular classification of breast cancer(P=0.046 and P=0.016).Binary logistic regression a-nalysis suggested that CD4+T cell percentage,DNT cell percentage,CEA,CA125,CA15-3 were the influencing factors for the occurrence of breast cancer.The differences were statistically significant(P=0.002,P<0.001,P=0.038,P=0.004 and P=0.013).ROC curve showed that the area under the curve of DNT cell percentage,CEA,CA125,CA15-3,CEA+CA125+CA15-3,DNT+CEA+CA125+CA15-3 was 0.810,0.702,0.714,0.727,0.812 and 0.897 in the healthy group and the breast cancer group,respectively.The area under the curve for benign and malignant breast tumors was 0.739,0.684,0.665,0.700,0.774 and 0.838,respectively.Conclusions There are significant differences in pe-ripheral blood T lymphocyte subsets between benign and malignant breast tumors,and DNT cells increased significantly in breast cancer patients.DNT cells and T lymphocyte subsets are statistically significant correlated with clinicopathologic features of breast cancer,and the combined detection of DNT cells and tumor markers CEA,CA125 and CA15-3 can im-prove the diagnostic efficiency of breast cancer.

breast cancerdouble-negative T cellsT lymphocyteflow cytometrydiagnostic index

钟振杰、武静、朱惠茹、刘晓斐

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锦州医科大学中国人民解放军联勤保障部队第九六○医院研究生培养基地,山东济南 250031

中国人民解放军联勤保障部队第九六○医院检验科,山东济南 250031

潍坊医学院医学检验学院,山东潍坊 261053

乳腺癌 双阴性T细胞 T淋巴细胞 流式细胞术 诊断指标

山东省自然科学基金面上项目

ZR2021MC137

2024

中华肿瘤防治杂志
中华预防医学会 山东省肿瘤防治研究院

中华肿瘤防治杂志

CSTPCD北大核心
影响因子:1.292
ISSN:1673-5269
年,卷(期):2024.31(8)
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