摘要
目的研究影响非小细胞肺癌吉非替尼敏感和耐药的临床特征,探讨敏感性患者和耐药性患者血清相关指标的水平变化。方法筛选口服吉非替尼敏感性患者58例,耐药患者72例,分析临床特征与耐药性的相关性。于清晨空腹抽取患者血液并提取血清。荧光定量PCR检测miR-140-5p、miR-155和miR-200c的表达情况以及Smad2 mRNA的水平;电化学发光免疫检测CEA含量;酶联免疫吸附试验检测TIMP-1和MMP-9的含量。结果患者是否吸烟和肿瘤分期在敏感性患者与耐药性患者中差异具有统计学意义。与敏感性患者相比,耐药患者miR-140-5p,miR-155和miR-200c的表达显著降低,Smad2的表达显著升高;与敏感性患者相比,耐药患者CEA含量显著升高,同时TIMP-1和MMP-9的含量也显著升高。结论吸烟是引起NSCLC患者耐药的一个重要因素,同时肿瘤分期也影响其耐药性;NSCLC临床治疗中,患者要尽早治疗,同时减少吸烟可以有效减少耐药性的产生。血清中CEA、Smad2、TIMP-1、MMP-9以及miR-140-5p、miR-155、miR-200c均可作为耐药性监测的辅助诊断指标,其含量对于耐药性患者的诊断和疗效监测具有重要意义。
Objective The aims of this study were to analyze the potential impacts of clinical characters, and explore the biomarkers＇ changes in serum between gefitinib-sensitive and resistant patients with non-small cell lung cancer（NSCLC）. Methods A total of 58 sensitive patients and 72 resistant patients were enrolled in the present study. Their clinical characters were recorded for analyzing the correlation between gefitinibsensitivity and resistance. The blood samples of all participants were obtained by fasting approach. The expression levels of miR-140-5p,miR-155,miR-200c and Smad2 mRNA were determined using real-time PCR. The level of CEA was measured using electrochemiluminescence immunoassay. Enzyme-linledimmune sorbent assay（ELISA）was performed to detect the level of TIMP-1 and MMP-9. Results The patients with smoking and high tumor stage showed significant correlation with gefitinib-resistance. Comparing with gefitinib-sensitive patients, the expressions of miR-140-5p, miR-155 and miR-200c were significantly decreased,while the expression of Smad2 was dramatically increased in resistant patients. Additionally, in comparison with gefitinib-sensitive patients, the levels of CEA, TIMP-1 and MMP-9 were all significantly increased in resistant patients. Conclusion Smoking and tumor stage affect gefitinib-resistance. In NSCLC clinical treatment, patients should be treated as early as possible, while reducing smoking can effectively reduce the production of drug resistance. Levels of CEA, Smad2, TIMP-1, MMP-9 and miR-140-5p in serum,also miR-155 and miR-200c can all be used as an auxiliary diagnostic index for drug resistance monitoring, and its content is of great significance for the diagnosis and therapeutic monitoring among drug resistant patients.
出处
《标记免疫分析与临床》
CAS
2018年第2期162-166,共5页
Labeled Immunoassays and Clinical Medicine
关键词
非小细胞肺癌
吉非替尼
耐药性
标志物
Non- small cell lung cancer
Gefitinib
Drug resistance
Biomarker
