T淋巴细胞衰老与老年人非小细胞肺癌的相关性研究
摘要
目的:探讨T淋巴细胞表面分子CD28、CD95增龄性变化与老年人原发性非小细胞肺癌发生发展之间的内在联系及相关机制。
方法:应用五色免疫荧光标记流式细胞术和荧光定量实时聚合酶链反应法,对63例老年非小细胞肺癌患者(老年肺癌组)的外周血T淋巴细胞亚群数量以及表面分子CD28、CD95的蛋白表达率和mRNA含量进行检测,结果分别与老年健康组、老年肺良性病变组(老年非癌组)、年轻健康组、年轻肺良性病变组(年轻非癌组)以及年轻肺癌组进行对比分析,同时研究这些免疫指标与老年肺癌生物学行为之间的关系。
结果:
1.方差分析显示,老年肺癌组外周血中T细胞亚群CD28的蛋白表达率及mRNA含量均显著低于其余各组(P<0.01),而CD95的蛋白表达率及mRNA含量则显著高于其余各组(P<0.01);经SNK q法检验,老年健康组外周血中CD28的蛋白及mRNA表达量明显低于年轻健康组和年轻非癌组,而CD95的蛋白及mRNA表达量则明显高于年轻健康组和年轻非癌组;老年非癌组与老年健康组比较,两者表达差异均无统计学意义。
2.Logistic回归分析显示,年龄、CD28 mRNA含量、CD95 mRNA含量均与肺癌的发生有统计学关联(OR值分别为2.432、0.389、2.796,P值均<0.01),且CD28与CD95的mRNA含量具有负相关性(r = -0.373,P<0.01)。
3.T细胞表面分子CD28、CD95的蛋白表达率及mRNA含量均与老年肺癌的临床TNM分期、细胞分化程度以及淋巴结转移状态密切相关(P<0.05),而与病理类型无关(P>0.05)。
结论:呈增龄性改变的T细胞衰老相关分子CD28、CD95在老年人原发性非小细胞肺癌的形成和演变过程中发挥着重要的调控作用。
Objective: To investigate the relationship between age-related changes of CD28 and CD95 on T lymphocytes and the development of primary non-small cell lung cancer (NSCLC) in elderly.
Methods: The protein and mRNA expression of CD28 and CD95 in peripheral blood of 63 elderly patients with NSCLC aged≥60 years were measured by five-color flow cytometric immunofluorescence assay and fluorescent quantitation real-time polymerase chain reaction. 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled as controls. Meanwhile, the relationship between CD28/CD95 and clinical characteristics of NSCLC in elderly was analysed with statistics.
Results:
1. Our results showed decreased protein and mRNA expression of CD28 (P<0.01) on T cells and increased proteion and mRNA of CD95 (P<0.01) in peripheral blood of all elderly patients with NSCLC compared with the other groups. The protein and mRNA expression of CD28 in elderly healthy donors was significantly lower than those in young healthy donors and young patients with lung benign lesion, but the expression CD95 of young healthy donors were significantly higher than those in young healthy donors and young patients with lung benign lesion. There were no significantly statistic differences in expression of CD28 and CD95 between elderly healthy donors and elderly patients with lung benign lesion.
2. Logistic regression analysis showed that the increased risk for lung cancer were significantly associated with aging (OR=2.432), down-regulation of CD28 mRNA (OR=0.389) and up-regulation of CD95 mRNA (OR=2.796), and the mRNA expression of CD28 had significant negative correlation with the mRNA expression of CD95 (r = -0.373, P<0.01).
3. In the elderly patients with NSCLC, the protein and mRNA expression of CD28 and CD95 on T cells in peripheral blood was closely associated with TNM stages, grade of cell differentiation and lymph node metastasis status (P<0.05), but not related to pathological types (P>0.05).
Conclusions: The down-regulation of CD28 and up-regulation of CD95 with age on T cells in peripheral blood play an important role in the oncogenesis and development of primary NSCLC in elderly.
方法:应用五色免疫荧光标记流式细胞术和荧光定量实时聚合酶链反应法,对63例老年非小细胞肺癌患者(老年肺癌组)的外周血T淋巴细胞亚群数量以及表面分子CD28、CD95的蛋白表达率和mRNA含量进行检测,结果分别与老年健康组、老年肺良性病变组(老年非癌组)、年轻健康组、年轻肺良性病变组(年轻非癌组)以及年轻肺癌组进行对比分析,同时研究这些免疫指标与老年肺癌生物学行为之间的关系。
结果:
1.方差分析显示,老年肺癌组外周血中T细胞亚群CD28的蛋白表达率及mRNA含量均显著低于其余各组(P<0.01),而CD95的蛋白表达率及mRNA含量则显著高于其余各组(P<0.01);经SNK q法检验,老年健康组外周血中CD28的蛋白及mRNA表达量明显低于年轻健康组和年轻非癌组,而CD95的蛋白及mRNA表达量则明显高于年轻健康组和年轻非癌组;老年非癌组与老年健康组比较,两者表达差异均无统计学意义。
2.Logistic回归分析显示,年龄、CD28 mRNA含量、CD95 mRNA含量均与肺癌的发生有统计学关联(OR值分别为2.432、0.389、2.796,P值均<0.01),且CD28与CD95的mRNA含量具有负相关性(r = -0.373,P<0.01)。
3.T细胞表面分子CD28、CD95的蛋白表达率及mRNA含量均与老年肺癌的临床TNM分期、细胞分化程度以及淋巴结转移状态密切相关(P<0.05),而与病理类型无关(P>0.05)。
结论:呈增龄性改变的T细胞衰老相关分子CD28、CD95在老年人原发性非小细胞肺癌的形成和演变过程中发挥着重要的调控作用。
Objective: To investigate the relationship between age-related changes of CD28 and CD95 on T lymphocytes and the development of primary non-small cell lung cancer (NSCLC) in elderly.
Methods: The protein and mRNA expression of CD28 and CD95 in peripheral blood of 63 elderly patients with NSCLC aged≥60 years were measured by five-color flow cytometric immunofluorescence assay and fluorescent quantitation real-time polymerase chain reaction. 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled as controls. Meanwhile, the relationship between CD28/CD95 and clinical characteristics of NSCLC in elderly was analysed with statistics.
Results:
1. Our results showed decreased protein and mRNA expression of CD28 (P<0.01) on T cells and increased proteion and mRNA of CD95 (P<0.01) in peripheral blood of all elderly patients with NSCLC compared with the other groups. The protein and mRNA expression of CD28 in elderly healthy donors was significantly lower than those in young healthy donors and young patients with lung benign lesion, but the expression CD95 of young healthy donors were significantly higher than those in young healthy donors and young patients with lung benign lesion. There were no significantly statistic differences in expression of CD28 and CD95 between elderly healthy donors and elderly patients with lung benign lesion.
2. Logistic regression analysis showed that the increased risk for lung cancer were significantly associated with aging (OR=2.432), down-regulation of CD28 mRNA (OR=0.389) and up-regulation of CD95 mRNA (OR=2.796), and the mRNA expression of CD28 had significant negative correlation with the mRNA expression of CD95 (r = -0.373, P<0.01).
3. In the elderly patients with NSCLC, the protein and mRNA expression of CD28 and CD95 on T cells in peripheral blood was closely associated with TNM stages, grade of cell differentiation and lymph node metastasis status (P<0.05), but not related to pathological types (P>0.05).
Conclusions: The down-regulation of CD28 and up-regulation of CD95 with age on T cells in peripheral blood play an important role in the oncogenesis and development of primary NSCLC in elderly.
引文
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