Prognostic value of DNA repair genes in non-small cell lung squamous carcinoma patients received platinum-based chemotherapy

doi:10.3877/cma.j.issn.2095-5820.2020.01.002

Abstract

Abstract:

Objective

To explore the prognostic value of DNA repair genes in patients with different pathological types of non-small cell lung cancer (NSCLC) and were all received platinum-based chemotherapy.

Methods

Immunohistochemical technique was used to measure the expression levels of the following DNA repair genes: poly ADP-ribose polymerase gene 1 (PARP1), excision and repair of cross-complementing gene 1 (ERCC1), mismatch repair and homology type 2 gene (MSH2), breast cancer susceptibility gene 1 (BRCA1) in paraffin embedded lesions of 121 NSCLC patients received platinum-based chemotherapy. The relationship between the expression levels of DNA repair genes and clinicopathological features in NSCLC patients was analyzed. The prognostic value of DNA repair gene expression level in NSCLC patients with different pathological types and whether it is an independent prognostic index were determined by survival analysis.

Results

The expression of ERCC1, PARP1, BRCA1 and MSH2 in NSCLC was not correlated with gender, age, smoking index and clinical TNM staging (P>0.05). ERCC1, RARP1, BRCA1, and MSH2 were not independent prognostic factors in NSCLS adenocarcinoma patients (P>0.05). But ERCC1 and PARP1 were independent prognostic factors in NSCLS squamous patients (P=0.019, 0.031).

Conclusion

ERCC1 and PARP1 are independent prognostic markers of NSCLC SCC patients received platinum-based chemotherapy.

Key words: DNA repair gene, Non-small cell lung cancer, Chemotherapy, Squamous cell carcinoma, Prognosis

Kejie Xie, Honger He, Xingmu Wang, Meidan Wang, Dongdong Wu. Prognostic value of DNA repair genes in non-small cell lung squamous carcinoma patients received platinum-based chemotherapy[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2020, 08(01): 6-12.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhlcsysgldzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-5820.2020.01.002

https://zhlcsysgldzzz.cma-cmc.com.cn/EN/Y2020/V08/I01/6

Figures/Tables 7

References 13

1	Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer[J]. N Engl J Med, 2018,378(22):2078-2092.
2	Xie KJ, He HE, Sun AJ, et al. Expression of ERCC1,MSH2 and PARP1 in non-small cell lung cancer and prognostic value in patients treated with platinum-based chemotherapy[J]. Asian Pac J Cancer Prev, 2014,15(6):2591-2596.
3	Wallerek S, Sørensen JB. Biomarkers for efficacy of adjuvant chemotherapy following complete resection in NSCLC stages I-IIIA[J]. Eur Respir Rev, 2015,24(136):340-355.
4	Chen YY, Lin YJ, Huang WT, et al. Demethoxycurcumin-loaded chitosan nanoparticle downregulates DNA repair pathway to improve cisplatin-induced apoptosis in non-small cell lung cancer[J].Molecules, 2018,23(12).pii: E3217.
5	Apopa PL, Alley L, Penney RB, et al. PARP1 is up-regulated in non-small cell lung cancer tissues in the presence of the cyanobacterialtoxin microcystin[J]. Front Microbiol, 2018,9:1757.
6	丁剑午，唐罗勇，艾素芬，等. ERCC1、BRCA1、RRM1表达在晚期非小细胞肺癌个体化治疗中的前瞻性研究[J].中国当代医药,2017,32:56-58.
7	白娟，郑玲，李茨，等.联合检测ERCC1、BRCA1、RRM1表达在非小细胞肺癌选择化疗方案中的意义[J].现代肿瘤医学, 2016,21:3410-3413.
8	Pierceall WE, Olaussen KA, Rousseau V, et al. Cisplatin benefit is predicted by immunohistochemical analysis of DNA repair proteins in squamous cell carcinoma but not adenocarcinoma: theranostic modeling by NSCLC constituent histological subclasses[J].Annoncol, 2012,23(9):2245-2252.
9	Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma[J]. J Thorac Oncol, 2011,6:244-285.
10	Pereira TC, Share SM, Magalhaes AV, et al. Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohisto-chemical tissue microarray study of 194 cases[J]. Appl Immunohis-tochem Mol Morphol, 2011,19:10-14.
11	Terry J, Leung S, Laskin J, et al. Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples[J]. Am J Surg Pathol, 2010,34:1805-1811.
12	Jin G, Kim MJ, Jeon HS, et al. PTEN mutations and relationship to EGFR,ERBB2,KRAS,and TP53 mutations in non-small cell lung cancers[J]. Lung Cancer, 2010,69:279-283.
13	Christopoulos P, Kirchner M, Endris V, et al. EML4-ALK V3, treatment resistance,and survival: refining the diagnosis of ALK⁺ NSCLC[J]. J Thorac Dis, 2018,10(Suppl 17):S1989-S1991.

临床特征		例数	ERCC1			阴性	PARP1		阴性	BRCA1		阴性	MSH2
临床特征		例数	阴性	阳性	P值	阴性	阳性	P值	阴性	阳性	P值	阴性	阳性	P值
性别		?	?	?	?	?	?	?	?	?	?	?	?	?
?	男	70	46	24	0.348	30	40	0.144	50	20	0.331	43	27	0.447
?	女	51	29	22	?	29	22	?	32	19	?	35	16	?
吸烟指数		?	?	?	?	?	?	?	?	?	?	?	?	?
?	<400	68	38	30	0.134	30	38	0.275	44	24	0.44	48	20	0.128
?	≥400	53	37	16	?	29	24	?	38	15	?	30	23	?
年龄（岁）		?	?	?	?	?	?	?	?	?	?	?	?	?
?	<60	71	42	29	0.569	38	33	0.711	52	19	0.167	49	22	0.249
?	≥60	50	33	17	?	21	29	?	30	20	?	29	21	?
TNM分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	I	46	30	16	0.883	24	22	0.064	29	17	0.473	31	15	0.562
?	II	35	21	14	?	18	27	?	23	12	?	20	15	?
?	III+IV	40	24	16	?	25	13	?	30	10	?	27	13	?
T分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	T1	49	29	20	0.655	27	22	0.090	30	19	0.271	26	23	0.097
?	T2	43	29	14	?	23	20	?	33	10	?	31	12	?
?	T3+T4	29	17	12	?	9	20	?	19	10	?	21	8	?
N分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	N0	45	27	18	0.951	23	22	0.714	29	16	0.725	29	16	0.604
?	N1	38	23	15	?	20	18	?	27	11	?	26	12	?
?	N2	29	19	10	?	13	16	?	21	8	?	19	10	?
?	N3	9	6	3	?	3	6	?	5	4	?	4	5	?
M分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	M0	95	62	33	0.155	45	50	0.558	63	32	0.416	65	30	0.769
?	M1	26	13	13	?	14	12	?	15	11	?	17	9	?
病理类型		?	?	?	?	?	?	?	?	?	?	?	?	?
?	腺癌	59	41	18	0.391	26	33	0.413	38	21	0.401	40	19	0.811
?	鳞癌	57	32	25	?	31	26	?	39	18	?	39	18	?
?	其他	5	3	2	?	3	2	?	2	3	?	4	1	?

临床特征		例数	ERCC1			阴性	PARP1		阴性	BRCA1		阴性	MSH2
临床特征		例数	阴性	阳性	P值	阴性	阳性	P值	阴性	阳性	P值	阴性	阳性	P值
性别		?	?	?	?	?	?	?	?	?	?	?	?	?
?	男	70	46	24	0.348	30	40	0.144	50	20	0.331	43	27	0.447
?	女	51	29	22	?	29	22	?	32	19	?	35	16	?
吸烟指数		?	?	?	?	?	?	?	?	?	?	?	?	?
?	<400	68	38	30	0.134	30	38	0.275	44	24	0.44	48	20	0.128
?	≥400	53	37	16	?	29	24	?	38	15	?	30	23	?
年龄（岁）		?	?	?	?	?	?	?	?	?	?	?	?	?
?	<60	71	42	29	0.569	38	33	0.711	52	19	0.167	49	22	0.249
?	≥60	50	33	17	?	21	29	?	30	20	?	29	21	?
TNM分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	I	46	30	16	0.883	24	22	0.064	29	17	0.473	31	15	0.562
?	II	35	21	14	?	18	27	?	23	12	?	20	15	?
?	III+IV	40	24	16	?	25	13	?	30	10	?	27	13	?
T分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	T1	49	29	20	0.655	27	22	0.090	30	19	0.271	26	23	0.097
?	T2	43	29	14	?	23	20	?	33	10	?	31	12	?
?	T3+T4	29	17	12	?	9	20	?	19	10	?	21	8	?
N分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	N0	45	27	18	0.951	23	22	0.714	29	16	0.725	29	16	0.604
?	N1	38	23	15	?	20	18	?	27	11	?	26	12	?
?	N2	29	19	10	?	13	16	?	21	8	?	19	10	?
?	N3	9	6	3	?	3	6	?	5	4	?	4	5	?
M分期		?	?	?	?	?	?	?	?	?	?	?	?	?
?	M0	95	62	33	0.155	45	50	0.558	63	32	0.416	65	30	0.769
?	M1	26	13	13	?	14	12	?	15	11	?	17	9	?
病理类型		?	?	?	?	?	?	?	?	?	?	?	?	?
?	腺癌	59	41	18	0.391	26	33	0.413	38	21	0.401	40	19	0.811
?	鳞癌	57	32	25	?	31	26	?	39	18	?	39	18	?
?	其他	5	3	2	?	3	2	?	2	3	?	4	1	?

病理类型	ERCC1				PARP1				BRCA1				MSH2
病理类型	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P
腺癌组	39	51	2.559	0.156	44	46	0.091	0.703	42	46	1.107	0.293	37	42	1.084	0.298
鳞癌组	22	45	8.441	0.004	30	49	6.851	0.009	43	46	1.065	0.306	38	40	0.543	0.361

病理类型	ERCC1				PARP1				BRCA1				MSH2
病理类型	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P	阳性中位生存时间（月）	阴性中位生存时间（月）	χ²	P
腺癌组	39	51	2.559	0.156	44	46	0.091	0.703	42	46	1.107	0.293	37	42	1.084	0.298
鳞癌组	22	45	8.441	0.004	30	49	6.851	0.009	43	46	1.065	0.306	38	40	0.543	0.361

临床特征		例数	中位生存时间	Log-rank卡方值	P值
性别		?	?	?	?
?	男	32	38	0.818	0.390
?	女	25	42	?	?
吸烟指数		?	?	?	?
?	<400	31	43	0.920	0.324
?	≥400	26	38	?	?
年龄(岁)		?	?	?	?
?	<60	18	46	2.732	0.125
?	≥60	39	36	?	?
TNM分期		?	?	?	?
?	I	15	50	11.033	0.004
?	II	25	38	?	?
?	III+IV	17	26	?	?
T分期		?	?	?	?
?	T1	17	51	6.674	0.027
?	T2	26	42	?	?
?	T3+T4	14	33	?	?
N分期		?	?	?	?
?	N0	16	45	8.189	0.019
?	N1	20	37	?	?
?	N2	18	32	?	?
?	N3	3	17	?	?
M分期		?	?	?	?
?	M0	38	39	9.156	0.010
?	M1	19	24	?	?

Please choose a citation manager

Content to export