非小细胞肺癌患者外周血miR-146a水平检测及临床意义
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摘要
目的探讨非小细胞肺癌(NSCLC)患者外周血miR-146a水平检测及其与肿瘤恶性程度的相关性。方法选取2015年1月至2017年10月间延安大学附属医院收治的接受根治性手术的80例NSCLC患者作为NSCLC组,同期选取确诊为良性病变且进行手术治疗的90例肺部小结节患者作为对照组。比较两组患者术前外周血中miR-146a表达水平、免疫逃逸指标水平以及术中所得肺部病灶中原癌基因表达量的差异,分析NSCLC患者外周血miR-146a水平与肿瘤恶性程度的相关关系。结果 NSCLC组患者外周血中miR-146a表达水平高于对照组患者;外周血中免疫逃逸指标CD4+CD25+调节性T细胞和CD8+CD25+抑制性T细胞的分布比例均高于对照组患者,自然杀伤细胞(NK)的分布比例低于对照组患者;病灶组织中原癌基因Wip1、Pim-1、pokemon和C-Myc mRNA的表达量均高于对照组患者,差异均有统计学意义(均P <0. 05)。NSCLC患者外周血miR-146a水平与机体免疫逃逸程度及原癌基因表达量均直接相关,差异均有统计学意义(均P <0. 05)。结论NSCLC患者外周血miR-146a异常高表达,与肿瘤细胞的免疫逃逸及原癌基因表达量均直接相关,是客观反映肿瘤恶性程度的可靠指标。
Objective To detect level of microRNA-146 a in peripheral blood in non-small cell lung cancer( NSCLC) and its correlation with grading of malignancy. Methods Eighty patients with NSCLC who underwent surgical treatment between January 2015 and October 2017 at Yan'an University Affiliated Hospital were selected as NSCLC group,and 90 patients with benign lung lesions undergoing operation at the same time were selected as the control group. The expression of microRNA-146 a in peripheral blood before operation,levels of immune escape indexes in peripheral blood and expression of proto-oncogene in lung lesions were compared between the two groups. The correlation between microRNA-146 a level in peripheral blood and grading of malignancy was analyzed. Results Expression level of microRNA-146 a was higherin NSCLC group than in the control group. Distribution ratio of CD4+CD25+regulatory T cells and CD8+CD25+inhibitory T cells were higher in NSCLC group than in the control group. Distribution ratio of natural killer( NK) cells was lower in NSCLC group than in the control group. The expression of proto-oncogenes such as Wip1、Pim-1、pokemon、C-Myc mRNA was higher in NSCLC group than in the control group( all P < 0. 05). Level of microRNA146 a in peripheral blood were directly correlated with the degree of immune escape and expression of proto-oncogene in NSCLC patients( all P < 0. 05). Conclusion Abnormal high expression of microRNA-146 a is directly related to immune escape of tumor cells and the expression of protooncogenes in NSCLC patients,and it is a reliable index to objectively reflect the degree of malignant tumors.
Objective To detect level of microRNA-146 a in peripheral blood in non-small cell lung cancer( NSCLC) and its correlation with grading of malignancy. Methods Eighty patients with NSCLC who underwent surgical treatment between January 2015 and October 2017 at Yan'an University Affiliated Hospital were selected as NSCLC group,and 90 patients with benign lung lesions undergoing operation at the same time were selected as the control group. The expression of microRNA-146 a in peripheral blood before operation,levels of immune escape indexes in peripheral blood and expression of proto-oncogene in lung lesions were compared between the two groups. The correlation between microRNA-146 a level in peripheral blood and grading of malignancy was analyzed. Results Expression level of microRNA-146 a was higherin NSCLC group than in the control group. Distribution ratio of CD4+CD25+regulatory T cells and CD8+CD25+inhibitory T cells were higher in NSCLC group than in the control group. Distribution ratio of natural killer( NK) cells was lower in NSCLC group than in the control group. The expression of proto-oncogenes such as Wip1、Pim-1、pokemon、C-Myc mRNA was higher in NSCLC group than in the control group( all P < 0. 05). Level of microRNA146 a in peripheral blood were directly correlated with the degree of immune escape and expression of proto-oncogene in NSCLC patients( all P < 0. 05). Conclusion Abnormal high expression of microRNA-146 a is directly related to immune escape of tumor cells and the expression of protooncogenes in NSCLC patients,and it is a reliable index to objectively reflect the degree of malignant tumors.
引文
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[14] Shiozawa M,Chang CH,Huang YC,et al. Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells[J]. BMC Immunol,2018,19:27.
[15] Zhao M,Zhang H,Zhu G,et al. Association between overexpression of Wip1 and prognosis of patients with non-small cell lung cancer[J]. Oncol Lett,2016,11:2365-2370.
[16]何亚洲,温桂兰.原癌基因Pim-1在非小细胞肺癌中的表达及与细胞凋亡的关系[J].广东医学,2014,35:3085-3088.
[17] Zhang QL,Xing XZ,Li FY,et al. Pretreatment pokemon level as a predictor of response to cisplatin and paclitaxel in patients with unresectable non-small cell lung cancer[J]. Oncol Res Treat,2015,38:496-502.
[18] Zuo Y,Yang D,Yu Y,et al. Niclosamide enhances the cytotoxic effect of cisplatin in cisplatin-resistant human lung cancer cells via suppression of lung resistance-related protein and c-myc[J]. Mol Med Rep,2018,17:3497-3502.
[2]王文然,戴月梅,玛依努尔·艾力. RRM1与BRCA1在晚期非小细胞肺癌患者中的表达及与吉西他滨联合卡铂化疗预后的相关性[J].中国肿瘤临床与康复,2017,24:1028-1031.
[3]邹勇,余昌文.肿瘤组织和血浆miR-146a表达水平与肝内胆管癌患者临床病理特征及预后相关性分析[J].河北医学,2018,24:357-360.
[4]付明刚,迪丽米娜·伊拉木,郭丽英. miR-146a在早期乳腺浸润性导管癌组织中的表达及临床意义[J].新疆医科大学学报,2018,41:715-718.
[5] Nikoli ZZ,Savi Pavi evi DL,Vu ic NL,et al. Association between a genetic variant in the hsa-miR-146a gene and cancer risk:An updated meta-analysis[J]. Cancer Causes Control,2014,25:1571-1575.
[6]陈少婷,郑振威,陈发林.非小细胞肺癌38例血清miR-21、miR-146a表达的临床意义[J].福建医药杂志,2016,38:69-72.
[7] Venkatesan S,Rosenthal R,Kanu N,et al. Perspective:APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution[J]. Ann Oncol,2018,29:563-572.
[8] Karagiannis P,Gilbert AE,Nestle FO,et al. IgG4 antibodies and cancer-associated inflammation:Insights into a novel mechanism of immune escape[J]. Oncoimmunology,2013,2:e24889.
[9] Ma QY,Huang DY,Zhang HJ,et al. Function and regulation of LAG3 on CD4+CD25-T cells in non-small cell lung cancer[J]. Exp Cell Res,2017,360:358-364.
[10]奉林.晚期非小细胞肺癌患者外周血CD4~+CD25~+FOXP3~+调节性T细胞的表达及临床意义[J].中国肿瘤临床与康复,2016,23:134-137.
[11] Trujillo-Ochoa JL,Corral-Jara KF,Charles-Ni1o CL,et al. Conjugated bilirubin upregulates TIM-3 expression on CD4+CD25+T Cells:Anti-inflammatory implications for hepatitis a virus infection[J]. Viral Immunol,2018,31:223-232.
[12]黄丽斌,石磊,杨卫兵.非小细胞肺癌抗肿瘤免疫应答与免疫逃逸相关研究[J].贵州医药,2014,38:172-175.
[13] Canter RJ,Murphy WJ. A possible new pathway in natural killer cell activation also reveals the difficulty in determining human NK cell function in cancer[J]. J Immunother Cancer,2018,6:79.
[14] Shiozawa M,Chang CH,Huang YC,et al. Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells[J]. BMC Immunol,2018,19:27.
[15] Zhao M,Zhang H,Zhu G,et al. Association between overexpression of Wip1 and prognosis of patients with non-small cell lung cancer[J]. Oncol Lett,2016,11:2365-2370.
[16]何亚洲,温桂兰.原癌基因Pim-1在非小细胞肺癌中的表达及与细胞凋亡的关系[J].广东医学,2014,35:3085-3088.
[17] Zhang QL,Xing XZ,Li FY,et al. Pretreatment pokemon level as a predictor of response to cisplatin and paclitaxel in patients with unresectable non-small cell lung cancer[J]. Oncol Res Treat,2015,38:496-502.
[18] Zuo Y,Yang D,Yu Y,et al. Niclosamide enhances the cytotoxic effect of cisplatin in cisplatin-resistant human lung cancer cells via suppression of lung resistance-related protein and c-myc[J]. Mol Med Rep,2018,17:3497-3502.