外周血T淋巴细胞亚群与不同分子分型乳腺癌患者无病生存的相关性研究

Effect of T-lymphocyte subpopulations in peripheral blood on disease-free survival of patients with different molecular subtypes of breast cancer

目的:观察不同分子分型浸润性乳腺癌患者外周血T淋巴细胞亚群的表达情况,分析乳腺癌患者免疫状态与不同分子分型乳腺癌的相关性。方法:选取2008年1月至2009年8月初诊于天津医科大学肿瘤医院乳腺中心的患者372例。均对入组患者采血,采用流式细胞术分析外周血的T淋巴细胞的亚群CD4+T细胞、CD8+T细胞、调节性T细胞(Treg细胞)及自然杀伤(NK)细胞水平。分析CD4+/CD8+比值的大小、调节性T细胞、自然杀伤细胞的免疫相关指标与乳腺癌不同分子分型Luminal A、Luminal B、HER-2过表达型以及三阴性乳腺癌患者临床病理特征之间的相关性。结果:372例乳腺癌患者中,Luminal A型为133例(35.8%)、Luminal B型为124例(33.3%)、HER-2过表达型为48例(12.9%)、三阴性为67例(18.0%)。在三阴性乳腺癌中外周血CD4+/CD8+比值越高,患者的无病生存时间越长(P<0.05),Treg细胞含量越低,患者的无病生存时间也越长(P<0.05),但CD4+/CD8+比值与Treg细胞含量并非三阴性乳腺癌无病生存的独立预后因素。而其他三种类型的乳腺癌中,CD4+/CD8+比值、Treg细胞含量与患者无病生存率无关(P>0.05)。NK细胞含量与以上4种分子分型乳腺癌患者的无病生存率并无明显的相关性(P>0.05)。结论:外周血CD4+/CD8+比值、Treg细胞含量可有效预测三阴性乳腺癌的无病生存率,但并非其独立的预后因素。

Objective：To determine the distribution of T-lymphocyte subpopulations in peripheral blood and its relationship with disease-free survival （DFS） of patients with different molecular subtypes of invasive breast cancer （IBC）. Methods：Data and plasma samples of 372 female patients with IBC treated at Tianjin Medical University Cancer Hospital and Institute between January 2008 and August 2009 were obtained. CD4^＋/CD8^＋ratio and the amount of regulatory T cells （Treg cells） and natural killer cells （NK cells） were measured through flow cytometry. Results：A total of 133 （35.8%）, 124 （33.3%）, 48 （12.9%）, and 67 cases （18.0%） presented luminal type A, luminal type B, HER-2 over-expression, and triple-negative type breast cancer （TNBC）, respectively. In TNBC, a longer DFS was observed when the peripheral CD4^＋/CD8^＋ratio was high or when the level of Treg cells was low （CD4^＋/CD8^＋P〈0.05 and Treg P〈0.05）. However, CD4^＋/CD8^＋and Treg are not independent prognostic factors for the DFS of TNBC cases. In other molecular subtypes of breast cancer, CD4^＋/CD8^＋ratio and the amount of Treg cells are not correlated with DFS （P〉0.05）. The level of NK cells is unrelated to the DFS of breast cancer with the four molecular subtypes （P〉0.05）. Conclusion：CD4^＋/CD8^＋ratio and the amount of Treg cells in peripheral blood may predict DFS of TNBC but are not considered as independent prognostic factors.