肿瘤浸润中性粒细胞在非小细胞肺癌转移中的作用研究

发布时间：2018-04-03 12:02

本文选题：肿瘤浸润炎性细胞　切入点：肿瘤浸润中性粒细胞　出处：《山东大学》2015年硕士论文

【摘要】：背景：肿瘤转移是导致癌症相关死亡的首要原因。现有研究发现存在一种快速的机制,能够在肿瘤发展的早期阶段驱动肿瘤细胞发生播散。肿瘤相关的炎症和肿瘤的发展密切相关,尤其是肿瘤浸润的中性粒细胞、淋巴细胞和巨噬细胞。本文的主要目是研究非小细胞肺癌原发灶与转移灶中炎细胞浸润水平的差异,并探寻有促进肿瘤细胞转移作用的关键炎细胞亚型。此外,我们对关键的炎细胞亚型也进行了相关临床研究。方法：纳入本项回顾性研究的患者共82人,包括初次诊断时伴有远处转移并且原发灶与转移灶一并切除的非小细胞肺癌患者41人,和另外41位与之配对的未发生转移只切除原发灶的患者。应用免疫组织化学染色检测123例肿瘤组织(包括转移组原发灶和转移灶各41例、未转移组原发灶41例)中CD66b+中性粒细胞、CD8+T淋巴细胞、CD163+巨噬细胞、E-钙黏蛋白和CXCL5的浸润和表达水平。应用Pearson卡方检验或Fisher精确检验进行肿瘤浸润中性粒细胞和外周血中性粒细胞与临床病理特征的相关性研究。应用Wilcoxon符号秩和检验比较原发灶与转移灶间浸润炎细胞的分布差异,以及转移组与未转移组原发灶间的分布差异。Spearman秩检验用于多项相关性研究。所有统计学分析中,若p0.05则认为有统计学意义。结果：CD66b+中性粒细胞的肿瘤浸润水平在转移组患者的原发灶明显高于其转移灶(p0.001)和未转移组患者的原发灶(p0.001)。但是,CD8+T淋巴细胞(p=0.288,p=0.325)和CD163+巨噬细胞(p=0.726,p=0.975)并没有明显的浸润差异。此外,CD66b+中性粒细胞的肿瘤浸润水平和CXCL5的表达水平呈正相关(Spearman相关系数=0.505,p0.001),而与E-钙黏蛋白的表达呈负相关(Spearman相关系数=-0.479,p0.001)。同时,肿瘤浸润中性粒细胞的浸润水平和外周血中性粒细胞水平呈正相关(Spearman相关系数=-0.493,p0.001)。进一步的研究发现,肿瘤浸润中性粒细胞(Spearman相关系数=0.415,p0.001)和外周血中性粒细胞(Spearman相关系数=0.334,p=0.002)与阳性淋巴结转移个数均存在明显的相关性。结论：我们的研究表明CD66b+的中性粒细胞,作为关键的炎细胞亚型,主要在肿瘤的原发灶大量聚集,而以淋巴细胞和巨噬细胞为主的其他亚型炎细胞在原发灶和转移灶的浸润并没有明显差异。肿瘤浸润中性粒细胞,在一定程度上通过诱导上皮间质转化,对非小细胞肺癌患者的转移发挥了重要作用。此外,与肿瘤浸润中性粒细胞有明显相关性的外周血中性粒细胞,或许可以作为一项简单易行的非小细胞肺癌的转移监测指标。
[Abstract]:Background: tumor metastasis is the leading cause of cancer-related deaths.Current studies have found a rapid mechanism that drives the spread of tumor cells in the early stages of tumor development.Tumor-associated inflammation is closely related to tumor development, especially tumor infiltrating neutrophils, lymphocytes and macrophages.The main purpose of this paper is to study the difference of inflammatory cell infiltration between primary tumor and metastatic focus of non-small cell lung cancer (NSCLC) and to explore the key inflammatory cell subtypes which can promote the metastasis of NSCLC.In addition, we have also conducted clinical studies on key inflammatory cell subtypes.Methods: a total of 82 patients were included in this retrospective study, including 41 patients with non-small cell lung cancer (NSCLC) with distant metastasis at the initial diagnosis and resection of the primary tumor and metastasis.And 41 other matched patients who had no metastasis except the primary tumor.Immunohistochemical staining was used to detect 123 cases of tumor tissues, including 41 cases of primary tumor and 41 cases of metastatic focus in metastatic group.The infiltration and expression of E-cadherin and CXCL5 in CD66b neutrophils and CD8 T lymphocytes of CD163 macrophages.The correlation between tumor infiltrating neutrophils and peripheral blood neutrophils and clinicopathological features was studied by Pearson chi-square test or Fisher accurate test.Wilcoxon symbolic rank sum test was used to compare the distribution of infiltrative cells between primary focus and metastatic focus, and the distribution difference between metastatic group and non-metastatic group. Spearman rank test was used to study the correlation.In all statistical analysis, if p0.05 is considered to have statistical significance.Results the tumor infiltration level of neutrophils in the metastatic group was significantly higher than that in the metastatic group (p0.001) and in the non-metastatic group (p0.001).However, there was no significant difference in the infiltration of CD8 T lymphocytes between 0.288 and 0.325) and that of CD163 macrophages (P0. 726 and p0. 975).In addition, the tumor infiltration level of CD66b neutrophil was positively correlated with the expression level of CXCL5 and the correlation coefficient was 0.505p0.001and negatively correlated with the expression of E-cadherin.At the same time, the infiltration level of tumor infiltrating neutrophils was positively correlated with the level of peripheral blood neutrophils.Further studies showed that the Spearman correlation coefficient of tumor infiltrating neutrophils was 0.415 (p0.001) and that of peripheral blood neutrophilic neutrophils was 0.334p0.002), which was significantly correlated with the number of positive lymph node metastases.Conclusion: our results suggest that the neutrophils of CD66b, as a key subtype of inflammatory cells, are mainly concentrated in the primary focus of the tumor.However, the infiltration of other subtypes of inflammatory cells, mainly lymphocytes and macrophages, had no significant difference in primary and metastatic foci.Tumor infiltration of neutrophil plays an important role in metastasis of non-small cell lung cancer by inducing epithelial interstitial transformation to some extent.In addition, peripheral blood neutrophils, which have a significant correlation with tumor infiltrating neutrophils, may be a simple and easy marker for monitoring the metastasis of non-small cell lung cancer (NSCLC).
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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