Vav1蛋白在非小细胞肺癌浸润T细胞中的表达及意义

The significance and expression of Vav1 in infiltrating T lymphocytes from nonsmall cell lung cancer

目的:探讨Vav1蛋白在非小细胞肺癌(Nonsmall cell lung cancer,NSCLC)浸润T淋巴细胞中的表达及其临床病理意义。方法:收集天津医科大学附属肿瘤医院肺外科手术切除的新鲜肺癌标本40例,分离出肿瘤浸润T淋巴细胞(Tumor infiltrating lymphocyte,TIL-T),通过RT-PCR方法检测TIL-T中Vav1基因水平的表达;Western blot检测Vav1蛋白表达情况。并且总结40例患者的临床病理特征,SPSS17.0软件对数据进行统计分析,采用独立样本t检验及ANOVA方差分析法,分析TIL-T中Vav1的表达与NSCLC临床病理特征的关系。结果:TIL-T中Vav1的表达与NSCLC组织的分化程度和淋巴结转移相关(P<0.05),而与年龄、性别、组织类型和临床分期无相关性(P>0.05)。高、中、低分化组的肺癌标本TIL-T中Vav1基因的表达量2-△CT值分别为0.113±0.097,0.055±0.050及0.029±0.022,三组比较有差异(P=0.007);且三组肺癌标本TIL-T中Vav1蛋白的IOD值分别为0.543±0.323,0.425±0.331及0.153±0.150,差异有统计学意义(P=0.010)。有淋巴结转移组及无淋巴结转移组肺癌标本TIL-T中Vav1基因的表达量2-△CT值分别为0.039±0.051及0.072±0.059,两组比较有差异(P=0.048);且两组肺癌标本TIL-T中Vav1蛋白的IOD值分别为0.229±0.205及0.454±0.324,差异有统计学意义(P=0.024)。结论:TIL-T中Vav1的表达水平与NSCLC的生物学行为密切相关,有助于判断预后。TIL-T中Vav1表达水平与肿瘤分化程度呈正相关,与淋巴结转移率呈负相关。提示肺癌组织局部免疫耐受可能与TIL-T中Vav1表达水平降低有关,Vav1是评价NSCLC患者T细胞功能以及局部免疫状态的指标之一。

Objective：To explore the expression and clinicopathological significance of Vavl in the infiltrating T lymphocytes of nonsmall cell lung cancer patients. Methods ：40 operated NSCLC patients were involved2 Tumor infiltrating T lymphocytes （TIL-T） were separated from nonsmall cell lung cancer tissues. The expression levels of Vavl in TIL-T were detected by RT-PCR and Western blot respectively. We also summarized the clinicopathological characteristics of the patients with NSCLC and analyzed the correlations between the expression of Vavl in TIL-T and these various clinicopathological parameters. The SPSS17.0 software was used for statisti- cal analysis. The independent sample t-test and ANOVA variance analysis were used to analyse the relationship between the expression of Vavl in TIL-T and the clinicopathologieal characteristics of the patients with NSCLS. Results：The expression levels of Vavl in TIL- T were associated significantly with degree of differentiation in NSCLC＇ and lymph node metastasis （P 〈 0.05）, but were not associated with age, gender, histology and clinical stage （P 〉 0.05 ）. The expression quantity of Vavl gene in TIL-T from well, moderate and poor differentiation lung cancer specimens was 0. 113 ±0. 097,0. 055±0. 050 and 0. 029 ±0. 022, respectively. There was difference among three groups（P = 0. 007）. And IOD value of Vavl protein in TIL-T from well, moderate and poor differentiation lung cancer specimens was 0. 543±0. 323,0. 425 ±0. 331 and 0. 153 ±0. 150. The difference had statistical significance（P =0. 010）. The ex- pression quantity of Vavl gene in TIL-T from the groups with and without lymph node metastasis was 0. 039± 0. 051 and 0. 072±0. 059, respectively. There was difference between two groups （ P = 0. 048 ）. And IOD value of Vavl protein in TIL-T from the two groups was 0.229±0. 205 and 0. 454 ± 0. 324, respectively. There was statistical significance difference（ P = 0. 024）. Conclusion： The expression levels of Vavl in TIL-T are closely associated with biological behavior of NSCLC. This study demonstrates that the local immune tolerance state of lung cancer tissues might associated with the lower expression levels of Vavl in TIL-T. Vavl may be an im- portant factor to evaluate the local immune state of NSCLC.