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

doi:10.3760/cma.j.cn371439-20201026-00078

Abstract

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

Liu Pei, Pu Jiaze, Huang Wen, Wang Fei. Expression differences of miR-200c, miR-19a and miR-155 in gefitinib sensitive and drug resistant NSCLC patients and their effects on prognosis[J]. Journal of International Oncology, 2021, 48(7): 409-414.

Figures/Tables 5

References 26

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临床指标	敏感组 (n=36)	耐药组 (n=44)	χ²/t值	P值
性别
男	20(55.56)	27(61.36)	0.276	0.600
女	16(44.44)	17(38.64)
年龄(岁)
≤60	19(52.78)	24(54.55)	0.025	0.875
>60	17(47.22)	20(45.45)
吸烟
是	6(16.67)	18(40.91)	5.541	0.019
否	30(83.33)	26(59.09)
组织学分类
腺癌	33(91.67)	42(95.45)	0.054	0.817
其他	3(8.33)	2(4.55)
临床分期
Ⅲ期	26(72.22)	17(38.64)	8.984	0.003
Ⅳ期	10(27.78)	27(61.36)
分化程度
高分化	25(69.44)	16(36.36)	8.673	0.003
中、低分化	11(30.56)	28(63.64)
淋巴结转移
是	5(13.89)	17(38.64)	6.082	0.014
否	31(86.11)	27(61.36)
miR-200c	0.98±0.42	0.45±0.22	7.249	<0.001
miR-19a	0.27±0.13	0.10±0.04	8.222	<0.001
miR-155	1.07±0.49	0.27±0.12	10.467	<0.001

因素	β值	SE值	Wald值	OR值	95%CI	P值
吸烟	-1.036	0.316	10.751	0.355	0.149~0.845	<0.001
临床分期	-0.704	0.258	7.455	0.494	0.274~0.892	0.021
分化程度	1.802	0.374	23.216	6.062	3.258~11.279	0.013
淋巴结转移	-0.863	0.275	9.856	0.422	0.245~0.726	0.019
miR-200c	1.709	0.369	21.440	5.521	3.126~9.752	<0.001
miR-19a	1.683	0.324	26.996	5.384	2.947~9.836	<0.001
miR-155	1.672	0.319	27.488	5.325	3.058~9.274	<0.001

临床病理特征	例数	miR-200c	t值	P值	r值	miR-19a	t值	P值	r值	miR-155	t值	P值	r值
临床分期
Ⅲ期	43	0.78±0.30	3.230	0.002	-0.578	0.21±0.10	3.188	0.002	-0.612	0.72±0.32	3.123	0.003	-0.594
Ⅳ期	37	0.59±0.21				0.15±0.06				0.53±0.20
分化程度
高分化	41	0.77±0.35	2.586	0.012	0.610	0.22±0.11	4.009	<0.001	0.632	0.78±0.35	4.773	<0.001	0.594
中、低分化	39	0.60±0.22				0.14±0.06				0.47±0.21
淋巴结转移
是	22	0.53±0.25	2.902	0.005	-0.587	0.13±0.06	3.721	<0.001	-0.629	0.45±0.21	3.391	0.001	-0.614
否	58	0.75±0.32				0.20±0.08				0.70±0.32