国际肿瘤学杂志

国际肿瘤学杂志 ›› 2021, Vol. 48 ›› Issue (7): 409-414.doi: 10.3760/cma.j.cn371439-20201026-00078

• 论著 • 上一篇    下一篇

吉非替尼敏感与耐药NSCLC患者miR-200c、miR-19a、miR-155表达差异及其对患者预后的影响

刘佩, 蒲嘉泽(), 黄雯, 汪斐   

  1. 南京医科大学第四附属医院肿瘤科 210031
  • 收稿日期:2020-10-26 修回日期:2020-12-28 出版日期:2021-07-08 发布日期:2021-07-26
  • 通讯作者: 蒲嘉泽 E-mail:2950610899@qq.com
  • 基金资助:
    南京市卫生科技发展专项资金(YKK19149)

Expression differences of miR-200c, miR-19a and miR-155 in gefitinib sensitive and drug resistant NSCLC patients and their effects on prognosis

Liu Pei, Pu Jiaze(), Huang Wen, Wang Fei   

  1. Department of Oncology, Fourth Affiliated Hospital of Nanjing Medical University, Nanjing 210031, China
  • Received:2020-10-26 Revised:2020-12-28 Online:2021-07-08 Published:2021-07-26
  • Contact: Pu Jiaze E-mail:2950610899@qq.com
  • Supported by:
    Nanjing Health Science and Technology Development Special Fund(YKK19149)

RichHTML

14

PDF

164

摘要：

目的 探讨吉非替尼敏感与耐药非小细胞肺癌(NSCLC)患者miR-200c、miR-19a、miR-155表达差异,并分析miR-200c、miR-19a、miR-155表达差异对患者预后的影响。方法 选取2015年8月1日至2019年8月1日南京医科大学第四附属医院采用吉非替尼治疗的80例Ⅲ~Ⅳ期NSCLC患者作为研究对象,其中吉非替尼敏感患者36例,作为敏感组,吉非替尼耐药患者44例,作为耐药组。比较两组患者一般资料、血清miR-200c、miR-19a、miR-155水平,探究NSCLC患者吉非替尼敏感影响因素及血清miR-200c、miR-19a、miR-155与NSCLC患者临床病理特征的相关性。分析患者生存情况。结果 与耐药组比较,敏感组患者吸烟例数较少( χ2=5.541,P=0.019 )、临床分期Ⅲ期例数较多( χ2=8.984,P=0.003 )、分化程度高分化例数较多( χ2=8.673,P=0.003 )、淋巴结转移例数较少( χ2=6.082,P=0.014 )、血清miR-200c、miR-19a、miR-155水平均较高( t=7.249,P<0.001;t=8.222,P<0.001;t=10.467,P<0.001 )。多因素logistic回归分析显示,吸烟(OR=0.355,95%CI为0.149~0.845,P<0.001 )、临床分期(OR=0.494,95%CI为0.274~0.892,P=0.021 )、分化程度( OR=6.062,95%CI为3.258~11.279,P=0.013 )、淋巴结转移( OR=0.422,95%CI为0.245~0.726,P=0.019 )、血清miR-200c( OR=5.521,95%CI为3.126~9.752,P<0.001 )、miR-19a(OR=5.384,95%CI为2.947~9.836,P<0.001 )、miR-155(OR=5.325,95%CI为3.058~9.274, P<0.001 )水平均为NSCLC患者吉非替尼敏感的影响因素。血清miR-200c、miR-19a、miR-155水平与NSCLC患者临床分期(t=3.230, P=0.002, r=-0.578; t=3.188, P=0.002, r=-0.612; t=3.123,P=0.003,r=-0.594 )、分化程度(t=2.586,P=0.012,r=0.610;t=4.009, P<0.001,r=0.632; t=4.773, P<0.001,r=0.594 )、淋巴结转移( t=2.902, P=0.005, r=-0.587; t=3.721,P<0.001,r=-0.629; t=3.391, P=0.001, r=-0.614 )均显著相关。与miR-200c、miR-19a、miR-155低水平患者比较,miR-200c( 63.19% vs. 4.37%, χ2=32.562, P<0.001 )、miR-19a( 61.01%vs. 4.75%,χ2=37.807, P<0.001 )以及miR-155( 57.82%vs. 0, χ2=44.454, P<0.001 )高水平患者1年生存率均较高,差异均有统计学意义。结论 血清miR-200c、miR-19a、miR-155水平在吉非替尼敏感NSCLC患者中明显升高,是吉非替尼敏感的重要影响因素,且与NSCLC患者临床分期、分化程度、淋巴结转移密切相关,血清高水平患者预后较好。

关键词: 癌,非小细胞肺, 微RNAs, 吉非替尼, 敏感, 耐药

Abstract:

Objective To investigate the expression differences of miR-200c, miR-19a and miR-155 in gefitinib sensitive and resistant non-small cell lung cancer (NSCLC) patients, and to analyze the effects of miR-200c, miR-19a and miR-155 expression differences on the prognosis of patients.Methods From August 1, 2015 to August 1, 2019, 80 patients with stage Ⅲ-Ⅳ NSCLC who were treated with gefitinib in the Fourth Affiliated Hospital of Nanjing Medical University were selected as the research objects. Among them, 36 cases were sensitive to gefitinib as the sensitive group, and 44 cases were resistant to gefitinib as the drug-resistant group. The general data, serum levels of miR-200c, miR-19a and miR-155 were compared between the two groups, and the sensitive factors of gefitinib in NSCLC patients and the correlations between serum miR-200c, miR-19a, miR-155 and clinicopathological characteristics of NSCLC patients were explored. The survival of the patients was analyzed. Results Compared with the drug-resistant group, the number of smoking cases in the sensitive group was less (χ2=5.541, P=0.019), the number of clinical stage Ⅲ cases was more ( χ2=8.984, P=0.003), the number of well-differentiated cases was more (χ2=8.673, P=0.003), the number of patients with lymph node metastasis was less (χ2=6.082, P=0.014), and the levels of serum miR-200c, miR-19a and miR-155 were higher (t=7.249, P<0.001;t=8.222, P<0.001;t=10.467, P<0.001). Multivariate logistic regression analysis showed that smoking (OR=0.355, 95%CI: 0.149-0.845, P<0.001), clinical stage (OR=0.494, 95%CI: 0.274-0.892, P=0.021), degree of differentiation (OR=6.062, 95%CI: 3.258-11.279, P=0.013), lymph node metastasis (OR=0.422, 95%CI: 0.245-0.726, P=0.019), the levels of serum miR-200c (OR=5.521, 95%CI: 3.126-9.752, P<0.001), miR-19a (OR=5.384, 95%CI: 2.947-9.836, P<0.001) and miR-155 (OR=5.325, 95%CI: 3.058-9.274, P<0.001) were all influencing factors of gefitinib sensitivity in NSCLC patients. The levels of serum miR-200c, miR-19a and miR-155 were significantly correlated with clinical stage (t=3.230, P=0.002, r=-0.578; t=3.188, P=0.002, r=-0.612; t=3.123, P=0.003, r=-0.594), degree of differentiation (t=2.586, P=0.012, r=0.610; t=4.009, P<0.001,r=0.632; t=4.773, P<0.001,r=0.594) and lymph node metastasis (t=2.902, P=0.005, r=-0.587; t=3.721, P<0.001,r=-0.629; t=3.391, P=0.001, r=-0.614) of NSCLC patients. Compared with the patients with low levels of serum miR-200c, miR-19a and miR-155, the 1-year survival rates of the patients with high levels of serum miR-200c (63.19% vs. 4.37%, χ2=32.562, P<0.001), miR-19a (61.01%vs. 4.75%, χ2=37.807, P<0.001) and miR-155 (57.82%vs. 0, χ2=44.454, P<0.001) were higher, with statistically significant differences.Conclusion The levels of serum miR-200c, miR-19a and miR-155 are significantly increased in gefitinib-sensitive NSCLC patients, which are important influencing factors of gefitinib sensitivity, and are closely related to clinicopathological characteristics such as clinical stage, differentiation degree and lymph node metastasis of NSCLC patients, and the prognosis is better in patients with high serum levels.

Key words: Carcinoma,non-small-cell lung, MicroRNAs, Gefitinib, Sensitive, Drug resistance