子宫内膜癌患者miR-30b和miR-96水平及与预后的关系

林一禾; 庄晓苹; 金纬纬

doi:10.16766/j.cnki.issn.1674-4152.001734

子宫内膜癌患者miR-30b和miR-96水平及与预后的关系

doi: 10.16766/j.cnki.issn.1674-4152.001734

温州市中西医结合医院西医妇科，浙江温州 325000

基金项目:

浙江省医药卫生科技计划项目 2017KY630

详细信息

通讯作者:
林一禾，E-mail：lyp7101@163.com

中图分类号: R737.33 R730.43
计量
- 文章访问数: 216
- HTML全文浏览量: 76
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2019-09-09
- 网络出版日期: 2022-02-19

Expression of miR-30b and miR-96 in endometrial carcinoma and their relationship with prognosis

Western medicine gynecology of Western medicine Wenzhou integrated Chinese and Western medicine hospital, Wenzhou, Zhejiang 325000, China

摘要

摘要: 目的检测子宫内膜癌(endometrial cancer，EC)患者外周血单个核细胞(peripheral blood mononuclear cell，PBMC)miR-30b、miR-96水平，探究其与临床病理及预后的关系。方法选择2012年10月—2014年8月温州市中西医结合医院收治的EC患者及门诊健康体检者(对照组)各76例，荧光定量PCR检测PBMC中miR-30b、miR-96水平，Pearson法分析二者相关性，Kaplan-Meier法分析二者与5年生存率的关系；Cox分析不良预后的危险因素。结果 EC患者PBMC中miR-30b、miR-96水平均高于对照组(t=21.913、24.188，均P＜0.05)，二者呈正相关(r=0.553，P＜0.05)，均与病理分级、FIGO分期、肌层浸润及淋巴结转移有关(均P＜0.05)。miR-30b高表达者5年总生存率(16.13%)低于低表达者(66.67%，χ²=16.890，P＜0.05)；miR-96高表达者5年总生存率(18.18%)低于低表达者(67.44%，χ²=16.307，P＜0.05)。miR-30b、miR-96、FIGO分期、淋巴结转移是预后的影响因素(HR=2.861, 95% CI: 1.427~5.736；HR=1.973, 95% CI: 1.462~2.663；HR=2.235, 95% CI: 1.491~3.350；HR=2.439, 95% CI: 1.365~4.358；均P＜0.05)。结论 PMBC中miR-30b、miR-96高表达，与EC患者病理分级、FIGO分期、肌层浸润、淋巴结转移及5年生存率有关，是影响预后的独立危险因素。
- 子宫内膜癌 /
- 微小RNA-30b /
- 微小RNA-96
Abstract: Objective The levels of miR-30b and miR-96 in peripheral blood mononuclear cells (PBMC) in patients with endometrial carcinoma (EC) were detected to explore their relationship with clinicopathology and prognosis. Methods A total of 76 EC patients and healthy outpatients(control group)admitted to Wenzhou hospital of integrated traditional Chinese and western medicine were selected. The expression levels of miR-30b and miR-96 in PBMC were detected by fluorescence quantitative PCR, the correlation was analyzed by Pearson method, the relationships between miR-30b and miR-96 expression levels in PBMC and 5-year survival rate of EC patients were analyzed by Kaplan-Meier method, and the risk factors affecting the prognosis of EC patients were analyzed by Cox regression. Results The expression levels of miR-30b and miR-96 in PBMC of EC patients were higher than those of control group (t=21.913, 24.188, all P < 0.05). They were positively correlated (r=0.553, P < 0.05), and correlated with pathological grade, FIGO stage, depth of muscle invasion and lymph node metastasis (P < 0.05). The 5-year overall survival rate of patients with high expression of miR-30b (16.13%) was lower than that of patients with low expression (66.67%, χ²=16.890, P < 0.05). The 5-year overall survival rate of patients with high expression of miR-96 (18.18%) was lower than that of patients with low expression (67.44%, χ²=16.307, P < 0.05). Levels of miR-30b and miR-96, FIGO stage and lymph node metastasis in PMBC were independent risk factors affecting the prognosis of EC patients (HR=2.861, 95% CI: 1.427-5.736; HR=1.973, 95% CI: 1.462-2.663; HR=2.235, 95% CI: 1.491-3.350; HR=2.439, 95% CI: 1.365-4.358; all P < 0.05). Conclusion The miR-30b and miR-96 are highly expressed in PMBC, which are related to pathological grade, FIGO stage, muscle invasion, lymph node metastasis and 5-year survival rate of EC patients, and are independent risk factors for adverse prognosis of EC patients.
- Endometrial cancer /
- MicroRNA-30b /
- MicroRNA-96

HTML全文

图 1 EC患者PBMC中miR-30b与miR-96水平的相关性

下载: 全尺寸图片幻灯片

图 2 PBMC中miR-30b水平与EC患者5年生存率的关系

下载: 全尺寸图片幻灯片

图 3 PBMC中miR-96水平与EC患者5年生存率的关系

下载: 全尺寸图片幻灯片

表 1 EC患者与对照组PBMC中miR-30b、miR-96表达水平比较(x±s)

组别	例数	miR-30b	miR-96
对照组	76	1.12±0.21	1.06±0.19
EC组	76	2.46±0.49	2.57±0.51
t值		21.913	24.188
P值		＜0.001	＜0.001

下载: 导出CSV

表 2 PBMC中miR-30b、miR-96表达水平与EC患者临床病理参数的关系[例(%)]

项目		例数	miR-30b		χ²值	P值	miR-96		χ²值	P值
项目		例数	高表达(31例)	低表达(45例)	χ²值	P值	高表达(33例)	低表达(43例)	χ²值	P值
年龄(岁)	＜55	52	18(34.62)	34(65.38)	1.853	0.173	19(36.54)	33(63.46)	2.350	0.125
	≥55	24	13(54.17)	11(45.83)			14(58.33)	10(41.67)
BMI	≥24	39	16(41.03)	23(58.97)	0.036	0.849	19(48.72)	20(51.28)	0.526	0.468
	＜24	37	15(40.54)	22(59.46)			14(37.84)	23(62.16)
月经周期(d)	≥30	23	10(43.48)	13(56.52)	0.004	0.952	11(47.83)	12(52.17)	0.067	0.796
	＜30	53	21(39.62)	32(60.38)			22(41.51)	31(58.49)
病理类型	Ⅰ型	67	27(40.30)	40(59.70)	0.015	0.902	30(44.78)	37(55.22)	0.085	0.770
	Ⅱ型	9	4(44.44)	5(55.56)			3(33.33)	6(66.67)
病理分级(级)	1+2	61	19(31.15)	42(68.85)	9.960	0.002	22(36.07)	39(63.93)	5.374	0.020
	3	15	12(80.00)	3(20.00)			11(73.33)	4(26.67)
FIGO分期(期)	Ⅰ+Ⅱ	61	18(29.51)	43(70.49)	14.006	< 0.001	19(31.15)	42(68.85)	16.504	＜0.001
	Ⅲ+Ⅳ	15	13(86.67)	2(13.33)			14(93.33)	1(6.67)
肌层浸润深度	＜1/2	55	17(30.91)	38(69.09)	6.633	0.010	17(30.91)	38(39.09)	10.908	0.001
	≥1/2	21	14(66.67)	7(33.33)			16(76.19)	5(23.81)
淋巴结转移	有	14	12(85.71)	2(14.29)	12.151	< 0.001	13(92.86)	1(7.14)	14.694	＜0.001
	无	62	19(30.65)	43(69.35)			20(32.26)	42(67.74)

下载: 导出CSV

表 3 EC患者预后影响因素的赋值情况

项目	赋值
年龄	年龄≥55岁=1，年龄＜55岁=0
miR-30b	＞2.46=1，≤2.46=0
miR-96	＞2.57=1，≤2.57=0
病理分级	1+2级=0，3级=1
FIGO分期	Ⅰ+Ⅱ期=0，Ⅲ+Ⅳ期=1
肌层浸润	＜1/2=1，≥1/2=0
结局	死亡=1，截尾=0
淋巴结转移	有转移=1，无转移=0
BMI	≥24=1，＜24=0
月经周期	≥30 d=1，＜30 d=0
病理类型	Ⅰ型=1，Ⅱ型=0

下载: 导出CSV

表 4 EC患者预后影响的单因素分析

自变量	B	Wald χ²	SE	P值	HR值	95% CI
年龄	0.434	1.145	0.406	0.365	1.544	0.904~2.637
miR-30b	1.425	5.376	0.615	＜0.001	4.158	1.875~9.221
miR-96	1.377	6.432	0.543	＜0.001	3.964	1.483~10.596
病理分级	1.229	5.725	0.514	＜0.001	3.417	1.619~7.212
FIGO分期	1.038	9.072	0.345	＜0.001	2.823	1.742~4.575
肌层浸润	0.656	4.631	0.305	0.024	1.928	1.257~2.957
淋巴结转移	1.153	7.496	0.421	＜0.001	3.169	2.114~4.751
BMI	0.445	1.431	0.372	0.296	0.641	0.277~1.482
月经周期	0.075	0.418	0.116	0.519	1.078	0.593~1.961
病理类型	0.185	0.727	0.217	0.428	0.831	0.418~1.652

下载: 导出CSV

表 5 EC患者预后影响的多因素Cox回归分析

自变量	B	Wald χ²	SE	P值	HR值	95% CI
miR-30b	1.051	5.476	0.499	0.001	2.861	1.427~5.736
miR-96	0.682	4.915	0.307	0.020	1.973	1.462~2.663
病理分级	0.427	1.736	0.324	0.084	1.533	0.886~2.652
FIGO分期	0.804	5.153	0.354	0.005	2.235	1.491~3.350
肌层浸润	0.348	1.352	0.299	0.164	1.416	0.893~2.245
淋巴结转移	0.892	4.486	0.421	0.011	2.439	1.365~4.358

下载: 导出CSV

参考文献(15)

[1]	郭玉霞, 郑绘霞. ING4在子宫内膜癌中的表达及意义[J]. 山西医科大学学报, 2018, 49(7): 859-861. https://www.cnki.com.cn/Article/CJFDTOTAL-SXYX201807024.htm
[2]	ZHANG K, LI H Y, YAN Y, et al. Identification of key genes and pathways between type Ⅰ and type Ⅱ endometrial cancer using bioinformatics analysis[J]. Oncol Lett, 2019, 18(3): 2464-2476. http://www.ingentaconnect.com/content/sp/ol/2019/00000018/00000003/art00039
[3]	WANG Q, ZHU W. MicroRNA-873 inhibits the proliferation and invasion of endometrial cancer cells by directly targeting hepatoma-derived growth factor[J]. Exp Ther Med, 2019, 18(2): 1291-1298. http://www.ingentaconnect.com/content/sp/etm/2019/00000018/00000002/art00055
[4]	VAN SINDEREN M, GRIFFITHS M, MENKHORST E, et al. Restoration of microRNA-29c in type Ⅰ endometrioid cancer reduced endometrial cancer cell growth[J]. Oncol Lett, 2019, 18(3): 2684-2693. http://www.researchgate.net/publication/334328349_Restoration_of_microRNA-29c_in_type_I_endometrioid_cancer_reduced_endometrial_cancer_cell_growth
[5]	周辉芳, 谢英, 孙殿兴. miR-30b的生物学功能研究进展[J]. 解放军医药杂志, 2019, 31(8): 108-111. https://www.cnki.com.cn/Article/CJFDTOTAL-HBGF201908027.htm
[6]	ZHANG K, WANG Y W, WANG Y Y, et al. Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling[J]. Gene, 2017, 619(1): 10-20. http://www.researchgate.net/profile/Ya_Wen_Wang/publication/315731133_Identification_of_microRNA_biomarkers_in_the_blood_of_breast_cancer_patients_based_on_microRNA_profiling/links/58eafcccaca2729d8cd59cbc/Identification-of-microRNA-biomarkers-in-the-blood-of-breast-cancer-patients-based-on-microRNA-profiling.pdf
[7]	JAYARAMAN M, RADHAKRISHNAN R, MATHEWS C A, et al. Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer[J]. Genes Cancer, 2017, 8(5-6): 566-576. doi: 10.18632/genesandcancer.144
[8]	DENNY L, QUINN M. FIGO cancer report 2015[J]. Int J Gynaecol Obstet, 2015, 131(2): 75.
[9]	周琦, 吴小华, 刘继红, 等. 子宫内膜癌诊断与治疗指南(第四版)[J]. 中国实用妇科与产科杂志, 2018, 34(8): 880-886. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF201808016.htm
[10]	许富, 崔德威. miR-30b的生物学功能研究进展[J]. 医学理论与实践, 2016, 29(11): 1434-1436. https://www.cnki.com.cn/Article/CJFDTOTAL-YXLL201611017.htm
[11]	LI Q, ZHANG X, LI N, et al. miR-30b inhibits cancer cell growth, migration, and invasion by targeting homeobox A1 in esophageal cancer[J]. Biochem Biophys Res Commun, 2017, 485(2): 506-512. doi: 10.1016/j.bbrc.2017.02.016
[12]	XU J, LV H, ZHANG B, et al. miR-30b-5p acts as a tumor suppressor microRNA in esophageal squamous cell carcinoma[J]. J Thorac Dis, 2019, 11(7): 3015-3029. doi: 10.21037/jtd.2019.07.50
[13]	QI Z, ZHANG B, ZHANG J, et al. MicroRNA-30b inhibits non-small cell lung cancer cell growth by targeting the epidermal growth factor receptor[J]. Neoplasma, 2018, 65(2): 192-200. doi: 10.4149/neo_2018_170217N118
[14]	WU L, PU X X, WANG Q Z, et al. miR-96 induces cisplatin chemoresistance in non-small cell lung cancer cells by downregulating SAMD9[J]. Oncol Lett, 2016, 11(2): 945-952. doi: 10.3892/ol.2015.4000
[15]	刘敏娟, 黄郁馨, 冯婉琴, 等. miR-96靶向血管生成素-1基因对子宫内膜异位症子宫内膜干细胞增殖的影响[J]. 广东医学, 2018, 39(23): 3448-3453. doi: 10.3969/j.issn.1001-9448.2018.23.002