Difference of the expressions of ER,VEGF and TGF-β1 between multiple EP and single EP patients and their prognosis analysis

doi:10.3969/j.issn.1673-8640.2019.05.007

Abstract

Abstract:

Objective To investigate the expression levels of estrogen receptor （ER）,vascular endothelial growth factor （VEGF）and transforming growth factor-beta 1（TGF-β1）in multiple endometrial polyp（EP）and single EP patients,and to analyze the relationship with prognosis. Methods A total of 100 premenopausal women undergoing hysteroscopic endometrial polypectomy were recruited. Among them,there were 50 multiple EP （>5） patients and 50 single EP patients. Totally,35 patients undergoing hysteroscopy due to oviductal problem were enrolled as normal endometrium group. Immunohistochemistry and reverse transcription polymerase chain reaction （RT-PCR） were used to determine the expression levels of ER,VEGF and TGF-β1 in normal endometrium,single EP and multiple EP groups. Kaplan-Meier curve was used to analyze the recurrence rate of EP patients. Cox regression analysis was used to assess the risk of EP recurrence. Results The mRNA and protein expression levels of ER,VEGF and TGF-β1 in the polyp tissues of multiple EP group and single EP group were higher than those in normal endometrium group （P<0.05）,and they were higher in multiple EP group than those in single EP group （P<0.05）. The recurrence rate in multiple EP group （42.0%） was higher than that in single EP group （12.0%）（P=0.001）. Cox regression analysis showed that endometriosis [hazard ratio（HR）=2.718,95% confidence interval（CI） 1.179-6.262] and multiple EP （HR=4.134,95%CI 1.663-10.273） were independent risk factors for EP recurrence,and the high expressions of VEGF （HR=1.073, 95%CI 1.014-1.136） and TGF-β1 （HR=1.056,95%CI 1.005-1.109）were independent risk factors for recurrence in multiple EP patients. Conclusions The high expressions of ER,VEGF and TGF-β1 in multiple EP group are closely related to the high recurrence rate after operation.

Key words: Estrogen receptor, Vascular endothelial growth factor, Transforming growth factor-beta 1, Endometrial polyp, Recurrence

CLC Number:

R446.1

DONG Huan, LIU Xiaoyi, CAI Yanqing, CHEN Xinliang, WANG Xianjing. Difference of the expressions of ER,VEGF and TGF-β1 between multiple EP and single EP patients and their prognosis analysis[J]. Laboratory Medicine, 2019, 34(5): 415-420.

Figures/Tables 7

References 19

[1]	SALIM S,WON H,NESBITT-HAWES E,et al.Diagnosis and management of endometrial polyps:a critical review of the literature[J]. J Minim Invasive Gynecol, 2011,18(5):569-581.
[2]	BOSTEELS J,KASIUS J,WEYERS S,et al. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities[J]. Cochrane Database Syst Rev,2015,11(2):CD009461.
[3]	YANG J H,YANG P K,CHEN M J,et al.Management of endometrial polyps incidentally diagnosed during IVF:a case-control study[J]. Reprod Biomed Online,2017,34(3):285-290.
[4]	YANG J H,CHEN C D,CHEN S U,et al.Factors influencing the recurrence potential of benign endometrial polyps after hysteroscopic polypectomy[J]. PLoS One,2015,10(12):e0144857.
[5]	PAVONE M E.Predicting the recurrence of endometrial polyps:a commentary[J]. Fertil Steril,2018,109(3):445.
[6]	GU F,ZHANG H,RUAN S,et al.High number of endometrial polyps is a strong predictor of recurrence:findings of a prospective cohort study in reproductive-age women[J]. Fertil Steril,2018,109(3):493-500.
[7]	LENCI M A,NASCIMENTO V A,GRANDINI A B,et al.Premalignant and malignant lesions in endometrial polyps in patients undergoing hysteroscopic polypectomy[J]. Einstein (Sao Paulo),2014,12(1):16-21.
[8]	饶芸,谢红艳,张新清. ER-α、PR、Ki-67和VEGF在子宫内膜息肉术后复发的表达及意义[J]. 中国实用医药,2012,7(13):15-17.
[9]	DU H,TAYLOR H S.The role of hox genes in female reproductive tract development,adult function,and fertility[J]. Cold Spring Harb Perspect Med,2015,6(1):a023002.
[10]	WONG M,CRNOBRNJA B,LIBERALE V,et al.The natural history of endometrial polyps[J]. Hum Reprod,2017,32(2):340-345.
[11]	CLARK T J,STEVENSON H.Endometrial polyps and abnormal uterine bleeding (AUB-P):what is the relationship,how are they diagnosed and how are they treated?[J]. Best Pract Res Clin Obstet Gynaecol,2017,40:89-104.
[12]	周晓景,王芳,牛吉峰. 子宫内膜息肉中雌、孕激素受体基因表达对宫腔镜术后妊娠影响的研究[J]. 中国医药指南,2012,10(24):439-440.
[13]	李建青,丁鸿燕,叶银才. 子宫内膜异位症不孕患者卵泡液VEGF的变化及意义[J]. 检验医学,2013,28(3):233-235.
[14]	SONI U K,CHADCHAN S B,KUMAR V,et al.A high level of TGF-B1 promotes endometriosis development via cell migration,adhesiveness,colonization,and invasiveness[J]. Biol Reprod,2018. [Epub ahead of print]
[15]	JEON S H,CHAE B C,KIM H A,et al.Mechanisms underlying TGF-beta1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis[J]. J Leukoc Biol,2007,81(2):557-566.
[16]	左艳,闫彩平,邓鹏飞,等. 雌激素受体、孕激素受体及微血管密度在子宫内膜息肉不同部位和正常同期内膜上的表达研究[J]. 中国实用医药,2015,10(21):43-44.
[17]	刘文轩,王旭初. 宫腔镜下息肉摘除术治疗子宫内膜息肉的疗效观察及其对血管内皮生长因子的影响[J]. 中国内镜杂志,2012,18(9):923-926.
[18]	WANG N,ZHANG Y,LIU B.Demographic and clinical features of endometrial polyps in patients with endometriosis[J]. Biomed Res Int,2016,2016:1460793.
[19]	KITAYA K,TADA Y,TAGUCHI S,et al.Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps[J]. Hum Reprod,2012,27(12):3474-3480.

基因名称	引物序列（5'~3'）	片段长度（bp）
ER	上游引物：TTC TCG TGC CTT AGT CTC C;下游引物：TCA ATA GTT TCC ACC AAT C	460
VEGF	上游引物：TTG CCT TGC TGC TCT ACC TC;下游引物：TGC ATG GTG ATG TTG GAC TC	400
TGF-β1	上游引物：CCA GAT TGA GAC CCT CCT CA;下游引物：ATG CAA TGC TGT TCT TGC AG	930

基因名称	引物序列（5'~3'）	片段长度（bp）
ER	上游引物：TTC TCG TGC CTT AGT CTC C;下游引物：TCA ATA GTT TCC ACC AAT C	460
VEGF	上游引物：TTG CCT TGC TGC TCT ACC TC;下游引物：TGC ATG GTG ATG TTG GAC TC	400
TGF-β1	上游引物：CCA GAT TGA GAC CCT CCT CA;下游引物：ATG CAA TGC TGT TCT TGC AG	930

组别	例数	年龄（岁）	BMI（kg/m²）	AUB[例（%）]	不孕症[例（%）]	经产妇[例（%）]
多发EP组	50	35.0（31.0~38.3）	21.8（20.6~22.9）	17（34.0）	26（52.0）	29（58.0）
单发EP组	50	35.5（32.0~41.0）	21.5（20.2~22.7）	15（30.0）	22（44.0）	26（52.0）
统计值		-1.503	-0.600	0.184	0.641	0.364
P值		0.133	0.549	0.668	0.423	0.546
组别	子宫内膜异位症[例（%）]		子宫腺肌症[例（%）]	子宫肌瘤[例（%）]	PCOS[例（%）]	EP大小（cm）
多发EP组	10（20.0）		2（4.0）	6（12.0）	8（16.0）	1.05±0.44
单发EP组	7（14.0）		4（8.0）	5（10.0）	6（12.0）	1.24±0.54
统计值	0.638		0.702	0.102	0.332	3.124
P值	0.424		0.678	0.749	0.564	0.063

组别	例数	年龄（岁）	BMI（kg/m²）	AUB[例（%）]	不孕症[例（%）]	经产妇[例（%）]
多发EP组	50	35.0（31.0~38.3）	21.8（20.6~22.9）	17（34.0）	26（52.0）	29（58.0）
单发EP组	50	35.5（32.0~41.0）	21.5（20.2~22.7）	15（30.0）	22（44.0）	26（52.0）
统计值		-1.503	-0.600	0.184	0.641	0.364
P值		0.133	0.549	0.668	0.423	0.546
组别	子宫内膜异位症[例（%）]		子宫腺肌症[例（%）]	子宫肌瘤[例（%）]	PCOS[例（%）]	EP大小（cm）
多发EP组	10（20.0）		2（4.0）	6（12.0）	8（16.0）	1.05±0.44
单发EP组	7（14.0）		4（8.0）	5（10.0）	6（12.0）	1.24±0.54
统计值	0.638		0.702	0.102	0.332	3.124
P值	0.424		0.678	0.749	0.564	0.063

组别	例数	ER mRNA	VEGF mRNA	TGF-β1 mRNA
正常内膜组	35	0.91±0.38	0.93±0.35	0.86±0.08
单发EP组	50	1.72±0.54^*	1.48±0.19^*	1.29±0.14^*
多发EP组	50	2.09±0.40^*#	1.86±0.35^*#	1.38±0.07^*#