血清miR-193a-3p、ATF5水平与三阴性乳腺癌患者化疗疗效的相关性

doi:10.11958/20240854

摘要/Abstract

摘要：

目的探究血清miR-193a-3p、激活转录因子5（ATF5）表达水平与三阴性乳腺癌（TNBC）患者临床病理特征及化疗疗效的相关性。方法选取TNBC患者（研究组）和乳腺良性疾病患者（对照组）各120例，检测研究对象血清miR-193a-3p、ATF5水平，分析血清miR-193a-3p、ATF5与病理特征的关系。根据疗效将TNBC患者分为治疗无效组50例和治疗有效组70例，比较2组miR-193a-3p、ATF5表达水平，分析影响TNBC患者化疗疗效的因素。结果与化疗前相比，化疗后研究组血清miR-193a-3p水平升高，ATF5水平降低（P<0.05）。与对照组相比，化疗前研究组血清miR-193a-3p水平降低，ATF5水平升高（P<0.05）。肿瘤直径≥3 cm、淋巴结转移、组织学分级为中低级、临床分期Ⅲ期、Ki-67>30%者miR-193a-3p表达水平降低，ATF5表达水平升高（P<0.05）。TNBC患者中，与治疗有效组相比，治疗无效组血清miR-193a-3p水平降低，ATF5水平升高（P<0.05）。较低水平的miR-193a-3p、较高水平的ATF5、有淋巴结转移、肿瘤直径≥3 cm、组织学分级为中低级、TNM分期Ⅲ期是影响TNBC患者化疗疗效的危险因素（P<0.05）。结论 TNBC患者血清中低水平miR-193a-3p、高水平ATF5均是化疗疗效的危险因素。

关键词: 三阴性乳腺癌, 放化疗，辅助, 预后, 影响因素分析, 基因，肿瘤, miR-193a-3p, 激活转录因子5

Abstract:

Objective To explore the correlation between serum levels of miR-193a-3p, activated transcription factor 5 (ATF5), clinicopathological characteristics and chemotherapy efficacy in patients with triple negative breast cancer (TNBC). Methods A total of 120 patients with TNBC admitted to our hospital were collected as the research group. In the same period, 120 cases with benign breast disease in our hospital were selected as the control group. Serum levels of miR-193a-3p and ATF5 were detected, and the relationship between them and clinicopathological characteristics were detected in two groups. According to the therapeutic effect, TNBC patients were divided into the treatment ineffective group (n=50) and the treatment effective group (n=70). The expression levels of miR-193a-3p and ATF5 were compared between the two groups, and factors affecting the chemotherapy efficacy of TNBC patients were analyzed. Results Compared with before chemotherapy, the serum miR-193a-3p level increased and ATF5 level decreased in TNBC patients after chemotherapy (P<0.05). Compared with the control group, the serum miR-193a-3p level of TNBC patients decreased in the research group before chemotherapy, and ATF5 level increased (P<0.05). The expression level of miR-193a-3p was lower and the expression level of ATF5 was higher in patients with tumor diameter≥3 cm, lymph node metastasis, low histological grade, clinical stage Ⅲ and Ki-67>30% (P<0.05). In TNBC patients, compared with the treatment effective group, patients in the treatment ineffective group showed a decreased serum miR-193a-3p level and an increased ATF5 level (P<0.05). Lower level of miR-193a-3p, higher level of ATF5, lymph node metastasis, tumor diameter ≥ 3 cm, low histological grade, and TNM stage Ⅲ were risk factors affecting the efficacy of chemotherapy in TNBC patients (P<0.05). Conclusion Low level of miR-193a-3p and high level of ATF5 in the serum of TNBC patients are risk factors for chemotherapy efficacy.

Key words: triple negative breast neoplasms, chemoradiotherapy, adjuvant, prognosis, root cause analysis, genes, neoplasm, miR-193a-3p, activating transcription factor 5

中图分类号:

R737.9

图/表 4

参考文献 17

[1]	COUGHLIN S S. Epidemiology of breast cancer in women[J]. Adv Exp Med Biol, 2019, 1152(1):9-29. doi:10.1007/978-3-030-20301-6_2.
[2]	HOWARD F M, OLOPADE O I. Epidemiology of triple-negative breast cancer:a review[J]. Cancer J, 2021, 27(1):8-16. doi:10.1097/PPO.0000000000000500.
[3]	MEHRAJ U, DAR A H, WANI N A, et al. Tumor microenvironment promotes breast cancer chemoresistance[J]. Cancer Chemother Pharmacol, 2021, 87(2):147-158. doi:10.1007/s00280-020-04222-w.
[4]	何思思, 李国良, 黄鹏程. miR-193a-3p通过富亮氨酸α2糖蛋白1/鞘氨醇激酶1信号通路抑制口腔鳞状细胞癌增殖与侵袭[J]. 解剖学杂志, 2022, 45(6):532-536,550.
	HE S S, LI G L, HUANG P C. miR-193a-3p inhibits proliferation and invasion of oral squamous cell carcinoma by mediating leucine-rich alpha-2-glycoprotein-1/sphingosine kinase 1 signaling pathway[J]. Chinese Journal of Anatomy, 2022, 45(6):532-536,550. doi:10.3969/j.issn.1001-1633.2022.06.008.
[5]	刘晓娟, 王静, 张娟, 等. lncRNA ZFAS1靶向miR-193a-3p调控宫颈癌细胞Siha放射敏感性的分子机制研究[J]. 中国免疫学杂志, 2021, 37(2):195-200.
	LIU X J, WANG J, ZHANG J, et al. Molecular mechanism of lncRNA ZFAS1 targeting miR-193 a-3 p regulating radiation sensitivity of cervical cancer cell Siha[J]. Chinese Journal of Immunology, 2021, 37(2):195-200. doi:10.3969/j.issn.1000-484X.2021.02.013.
[6]	HE F, XIAO H, CAI Y, et al. ATF5 and HIF1α cooperatively activate HIF1 signaling pathway in esophageal cancer[J]. Cell Commun Signal, 2021, 19(1):53. doi:10.1186/s12964-021-00734-x.
[7]	帅煜, 冯光勇, 吴明娜, 等. ATF5在复发鼻咽癌组织中的表达及意义[J]. 遵义医学院学报, 2019, 42(2):177-181.
	SHUAI Y, FENG G Y, WU M N, et al. Expression and significance of ATF5 in recurrent nasopharyngeal carcinoma tissues[J]. Journal of Zunyi Medical University, 2019, 42(2):177-181. doi:10.3969/j.issn.1000-2715.2019.02.011.
[8]	马伟杰, 白金喜, 李江平, 等. miR-193a-3p通过LGR4/ATF4信号的上调促进成骨细胞分化[J]. 吉林医学, 2021, 42(10):2314-2317,2321.
	MA W J, BAI J X, LI J P, et al. MiR-193a-3p promotes osteoblast differentiation through upregulation of LGR4/ATF4 signaling[J]. Jilin Medical Journal, 2021, 42(10):2314-2317,2321. doi:10.3969/j.issn.1004-0412.2021.10.002.
[9]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2019年版)[J]. 中国癌症杂志, 2019, 29(8):609-679.
	Breast cancer Professional Committee of China Anti Cancer Association. Guidelines and specifications for diagnosis and treatment of breast cancer of China Anti Cancer Association (2019 version)[J]. China Oncology, 2019, 29(8):609-679.
[10]	EISENHAUER E A, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J]. Eur J Cancer, 2009, 45(2):228-247. doi:10.1016/j.ejca.2008.10.026.
[11]	ZHANG J, REN J, HAO S, et al. MiRNA-491-5p inhibits cell proliferation, invasion and migration via targeting JMJD2B and serves as a potential biomarker in gastric cancer[J]. Am J Transl Res, 2018, 10(2):525-534.
[12]	TAHIRI A, AURE M R, KRISTENSEN V N. MicroRNA networks in breast cancer cells[J]. Methods Mol Biol, 2018, 1711:55-81. doi:10.1007/978-1-4939-7493-1_4.
[13]	张亚洁, 陆思楚, 马成蕾, 等. miR-193a-3p在子宫内膜癌中的表达及临床病理的关系[J]. 医学研究杂志, 2022, 51(6):168-172.
	ZHANG Y J, LU S C, MA C L, et al. Expression of miR-193a -3p in endometrial carcinoma and its relationship with clinical pathology[J]. Journal of Medical Research, 2022, 51(6):168-172. doi:10.11969/j.issn.1673-548X.2022.06.035.
[14]	刘明胜, 陈文超, 蔡颖畅. 下调lncRNA DNM3OS通过靶向miR-193a-3p增强人直肠癌细胞系SW-480的放疗敏感性[J]. 基础医学与临床, 2022, 42(2):260-267.
	LIU M S, CHEN W C, CAI Y C. Down-regulation of lncRNA DNM3OS enhances radiotherapy sensitivity of human rectal cancer cell line SW-480 by targeting miR-193a-3p[J]. Basic & Clinical Medicine, 2022, 42(2):260-267. doi:10.3969/j.issn.1001-6325.2022.02.010.
[15]	GAITHER K A, WATSON C, MADARAMPALLI B, et al. Expression of activating transcription factor 5(ATF5) is mediated by microRNA-520b-3p under diverse cellular stress in cancer cells[J]. PLoS One, 2020, 15(6):e0225044. doi:10.1371/journal.pone.0225044.
[16]	ZHOU J, TIAN H, ZHI X, et al. Activating transcription factor 5(ATF5)promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer[J]. Cancer Cell Int, 2021, 21(1):660. doi:10.1186/s12935-021-02315-x.
[17]	杨凌辰, 经莉, 孙洁芸. ATF5在子宫内膜癌组织中的表达及其临床意义[J]. 徐州医科大学学报, 2023, 43(6):415-419.
	YANG L C, JING L, SUN J Y. Expression of ATF5 in endometrial cancer and its clinical significance[J]. Acta Academiae Medicinae Xuzhou, 2023, 43(6):415-419. doi:10.3969/j.issn.2096-3882.2023.06.005.

组别	miR-193a-3p			ATF5/（ng/L）
组别	化疗前	化疗后	t	化疗前	化疗后	t
对照组	1.03±0.18	-		23.65±3.72	-
研究组	0.36±0.16	0.51±0.13	7.965^＊＊	41.48±8.01	28.54±3.69	15.309^＊＊
t	29.389^＊＊			22.111^＊＊

组别	miR-193a-3p			ATF5/（ng/L）
组别	化疗前	化疗后	t	化疗前	化疗后	t
对照组	1.03±0.18	-		23.65±3.72	-
研究组	0.36±0.16	0.51±0.13	7.965^＊＊	41.48±8.01	28.54±3.69	15.309^＊＊
t	29.389^＊＊			22.111^＊＊

临床指标	n	miR-193a-3p	t	ATF5/（ng/L）	t
年龄
≥50岁	92	0.36±0.16	0.589	41.73±7.89	0.625
<50岁	28	0.38±0.18	0.589	40.65±8.50	0.625
月经情况
绝经前	32	0.37±0.15	0.308	41.15±8.30	0.267
绝经后	88	0.36±0.16	0.308	41.60±7.95	0.267
肿瘤直径
≥3 cm	66	0.30±0.09	5.455^＊＊	45.22±6.28	6.586^＊＊
<3 cm	54	0.45±0.19	5.455^＊＊	36.91±7.55	6.586^＊＊
淋巴结转移
是	71	0.28±0.07	8.154^＊＊	46.58±4.84	12.745^＊＊
否	49	0.49±0.18	8.154^＊＊	34.09±5.55	12.745^＊＊
组织学分级
高	22	0.59±0.18	6.823^＊＊	30.98±4.97	8.659^＊＊
中低	98	0.31±0.11	6.823^＊＊	43.84±6.54	8.659^＊＊
临床分期
Ⅱ期	37	0.51±0.20	8.266^＊＊	34.93±8.77	7.113^＊＊
Ⅲ期	83	0.30±0.09	8.266^＊＊	44.40±5.61	7.113^＊＊
Ki-67
≤30%	36	0.51±0.21	5.865^＊＊	35.41±9.57	6.236^＊＊
>30%	84	0.30±0.08	5.865^＊＊	44.08±5.53	6.236^＊＊

临床指标	n	miR-193a-3p	t	ATF5/（ng/L）	t
年龄
≥50岁	92	0.36±0.16	0.589	41.73±7.89	0.625
<50岁	28	0.38±0.18	0.589	40.65±8.50	0.625
月经情况
绝经前	32	0.37±0.15	0.308	41.15±8.30	0.267
绝经后	88	0.36±0.16	0.308	41.60±7.95	0.267
肿瘤直径
≥3 cm	66	0.30±0.09	5.455^＊＊	45.22±6.28	6.586^＊＊
<3 cm	54	0.45±0.19	5.455^＊＊	36.91±7.55	6.586^＊＊
淋巴结转移
是	71	0.28±0.07	8.154^＊＊	46.58±4.84	12.745^＊＊
否	49	0.49±0.18	8.154^＊＊	34.09±5.55	12.745^＊＊
组织学分级
高	22	0.59±0.18	6.823^＊＊	30.98±4.97	8.659^＊＊
中低	98	0.31±0.11	6.823^＊＊	43.84±6.54	8.659^＊＊
临床分期
Ⅱ期	37	0.51±0.20	8.266^＊＊	34.93±8.77	7.113^＊＊
Ⅲ期	83	0.30±0.09	8.266^＊＊	44.40±5.61	7.113^＊＊
Ki-67
≤30%	36	0.51±0.21	5.865^＊＊	35.41±9.57	6.236^＊＊
>30%	84	0.30±0.08	5.865^＊＊	44.08±5.53	6.236^＊＊

组别	n	miR-193a-3p	ATF5/（ng/L）
治疗有效组	70	0.47±0.11	38.16±5.47
治疗无效组	50	0.21±0.03	46.13±6.25
t		19.269^＊＊	7.413^＊＊