影响乳腺癌患者免疫状态的相关因素分析

发布时间：2018-09-10 06:04

【摘要】：背景：如今世界范围内,乳腺癌已经占到所有恶性肿瘤中的10%,排第三位,同时也是作为广大女性中最为常见的肿瘤之一,已经非常严重威胁到女性的身心健康。我们发现,其发生率以及死亡率在不同国家和地区,具有一定差别。往往发达国家,乳腺癌的患者大多数为绝经后的老年女性,而在我国,一半以上却为绝经前年轻女性。在发达国家,早期的筛查检测改良术后规范辅助治疗手段和死亡率的降低等原因,正在和其高的发病率相抵消。在我国,乳腺癌的发病率及病死率正呈现出逐年上升的趋势。肿瘤的发生,与机体的自我防护功能坍塌有着直接的关系,因而免疫学机制研究从未停止,并且日益深入：机体抗肿瘤免疫中,细胞免疫占着不可替代的主导地位,而T细胞亚群则是目前反映细胞免疫功能重要检测手段。临床上常见的CD4+T细胞和CD8+T细胞检测就是依据传统T淋巴细胞表面CD抗原的种类及表现出来相应不同差异的功能而划分的两大亚群。在机体健康状态下,体内的相应免疫细胞间相互作用和协作,以及T细胞内部几个亚群间为保持机体免疫平衡而维持着相应的比例,而当T淋巴亚群功能和数量发生异常,即当CD4/CD8比例失去控制的时候,NK等免疫细胞低下时,则提示患者机体免疫功能受到了抑制。目的：比较正常人与乳腺癌患者免疫功能状态的差异,不同临床特征的乳腺癌患者的T细胞亚群分布,化疗对乳腺癌患者的免疫功能的影响等,从而探讨影响乳腺癌患者免疫状态的相关因素。方法：搜集2012年1月～2014年6月在大连医科大学附属二院确诊的初治乳腺癌经根治术和规律辅助规范化化疗患者70例,采用流式细胞术(FCM)检测化疗前后外周血中T细胞亚群(CD3、CD4、CD8)及NK细胞水平,统计其年龄、Ki67、TNM分期、分子分型(ER、PR、Her-2等)及有无淋巴转移等临床特征,并与30位健康者比较,分析其T细胞亚群分布情况差异。结果：与健康人比较,乳腺癌患者CD4T细胞低下,CD8T细胞上升,CD4/CD8比值降低(P0.05),统计有显著差异。乳腺癌患者T细胞亚群分布受临床特征影响：Lumina型较非Lumina型组CD3值(66.93±9.30 vs 72.30±6.67),CD8值(28.73±8.98 vs 35.01±8.44),CD4/CD8值(1.44±0.58 vs 1.12±0.42),差异均有统计学意义。无淋巴结转移组较有淋巴结转移组CD4值(39.41±7.55 vs 33.88±8.61),CD4/CD8比值(1.50±0.56 vs 1.23±0.53),有淋巴结转移组较无转移组CD4及CD4/CD8匕值显著下降,差异有统计学意义。Ki67对CD4/CD8比值有影响,高增值组(1.19±0.53)较低增值组(1.47±0.57)明显降低,差异有统计学意义。年龄仅仅与CD3值相关：老年组(65.54±8.89)较青年组(70.93±8.26)下降,具有统计学差异。而TNMl临l床分期与T淋巴细胞亚群的分布无明显相关。进一步分析术后辅助化疗对早中期乳腺癌患者T细胞亚群的影响,发现CD3、CD8、NK值化疗后较化疗前显著升高,CD4/CD8比值化疗后(1.11±0.48)较化疗前(1.36±0.56)降低,差异统计学均有统计学意义。并且发现单药组(蒽环或紫杉类)化疗方案较联合组(蒽环类和紫杉类)方案有显著差异：两组中CD3、CD8化疗后均较化疗前显著升高,并且升高幅度(差值d)不同。而NK细胞在联合组化疗后呈显著升高,在单药组却呈现下降趋势。分析AC-T方案每周期T细胞亚群分布趋势,CD3、 CD4随化疗周期呈倒U改变。CD8值随周期进行呈明显上升趋势终趋于平稳。NK细胞数值随化疗周期呈波动型变化。结论：乳腺癌患者较健康人免疫功能下降,不同临床特征对早期乳腺癌患者T细胞亚群分布有差异,对NK细胞无明显影响：其中分子分型、淋巴结转移及Ki67与T细胞亚群相关,年龄及分期对T细胞亚群无显著影响。乳腺癌术后辅助化疗使CD3、CD8、NK均呈升高,CD4/CD8下降,免疫功能下降。不同种类化疗方案和化疗周期对T细胞亚群亦存在差异。化疗药物的选择及应用均是影响患者免疫状态的重要因素。监测患者T细胞亚群及NK细胞的表达水平可评估患者的细胞免疫状态,了解机体不同时段的免疫功能,对日后探究肿瘤病因、进展过程及临床上作为评价疗效的一种手段,都将给我们一定的启示,提供重要的线索和依据意义。
[Abstract]:BACKGROUND: Nowadays, breast cancer has accounted for 10% of all malignant tumors in the world, ranking the third. It is also one of the most common tumors among women. It has seriously threatened women's physical and mental health. We find that the incidence and mortality of breast cancer vary from country to country and region. In China, the incidence and mortality of breast cancer are offset by the high incidence of breast cancer in developed countries, where more than half of the patients are young women before menopause. The occurrence of tumors is directly related to the collapse of the body's self-protection function, so the study of immunological mechanism has never stopped and is deepening day by day. Cellular immunity plays an irreplaceable leading role in the body's anti-tumor immunity, while T cell subsets are currently important in reflecting the function of cellular immunity. Detection of CD4+T cells and CD8+T cells is based on the types of CD antigens on the surface of traditional T lymphocytes and their different functions. Objective: To compare the difference of immune function between normal people and breast cancer patients, and to compare the difference of immune function between normal people and breast cancer patients. Methods: To collect the data from January 2012 to June 2014 from the Second Affiliated Hospital of Dalian Medical University. The levels of T cell subsets (CD3, CD4, CD8) and NK cells in peripheral blood of 70 patients before and after chemotherapy were detected by flow cytometry (FCM). The clinical features of the patients, such as age, Ki67, TNM stage, molecular typing (ER, PR, Her-2, etc.) and lymphatic metastasis were analyzed. The distribution of T cell subsets was compared with 30 healthy subjects. The distribution of T lymphocyte subsets in breast cancer patients was affected by clinical characteristics: CD3 value (66.93 The CD4 value and CD4/CD8 dagger value in the group with lymph node metastasis were significantly lower than those in the group without lymph node metastasis (39.41+7.55 vs 33.88+8.61) and the ratio of CD4/CD8 (1.50+0.56 vs 1.23+0.53). The CD4 and CD4/CD8 dagger value in the group with lymph node metastasis were significantly lower than those in the group without lymph node metastasis (1.19+0.53). Age was only correlated with CD3. Age was significantly lower in the elderly group (65.54 + 8.89) than in the younger group (70.93 + 8.26). There was no significant correlation between the clinical stage of TNM and the distribution of T lymphocyte subsets. CD3, CD8 and NK were significantly higher after chemotherapy than before chemotherapy, and the ratio of CD4 to CD8 was significantly lower after chemotherapy than before chemotherapy (1.11 + 0.48) and the difference was statistically significant. CD8 increased significantly after chemotherapy, and the difference was different. NK cells increased significantly after chemotherapy in combination group, but showed a downward trend in single drug group. The distribution of T lymphocyte subsets in each cycle of AC-T regimen was analyzed. CD3 and CD4 showed an inverted U change with the chemotherapy cycle. CD8 value showed a significant upward trend and eventually leveled with the cycle. Conclusion: The immune function of breast cancer patients is lower than that of healthy people, and the distribution of T cell subsets in early breast cancer patients is different, but there is no significant effect on NK cells. After breast cancer surgery, adjuvant chemotherapy increased CD3, CD8 and NK, decreased CD4/CD8, and decreased immune function. Different chemotherapy regimens and chemotherapy cycles also had different effects on T cell subsets. The level can evaluate the patient's cellular immune status, understand the immune function of the body at different times, and explore the etiology of tumor, progress and clinical evaluation of curative effect as a means, will give us some inspiration, provide important clues and basis significance.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.9

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