转化生长因子-β1与胎盘生长因子在葡萄胎预后中的意义
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摘要
目的探讨转化生长因子-β1(TGF-β1)与胎盘生长因子(PLGF)在葡萄胎预后中的意义。方法收集180例葡萄胎患者,至少随访1年,其中30例发展为侵蚀性葡萄胎,1例发展为绒癌。采用免疫组化SV0002两步法检测33例正常早期妊娠(对照组)、33例未恶变葡萄胎(良性组)、31例恶变为妊娠滋养细胞肿瘤的葡萄胎(恶变组)的TGF-β1与PLGF的表达。结果恶变组TGF-β1阳性表达率(58.1%)低于对照组(97.0%)和良性组(87.9%),差异有统计学意义(P﹤0.05),对照组和良性组间差异无统计学意义(P﹥0.05);恶变组PLGF阳性表达率(90.3%)高于对照组(36.4%)和良性组(63.6%),差异有统计学意义(P﹤0.05),对照组和良性组间差异无统计学意义(P﹥0.05)。良性组和恶变组患者中年龄﹥40岁、人绒毛膜促性腺激素(h CG)﹥105U/L、子宫体积﹥孕周大小者TGF-β1阳性表达率均低于无上述高危因素者(P﹤0.05);卵巢黄素化囊肿直径﹥6 cm、重复性葡萄胎患者TGF-β1阳性表达率与无上述高危因素者比较,差异均无统计学意义(P﹥0.05)。良性组和恶变组患者中年龄﹥40岁、h CG﹥105U/L、子宫体积﹥孕周大小、卵巢黄素化囊肿直径﹥6 cm者的PLGF阳性表达率均高于无上述高危因素者(P﹤0.05);有无重复性葡萄胎者PLGF阳性表达率比较,差异无统计学意义(P﹥0.05)。良性组和恶变组中TGF-β1与PLGF表达均呈负相关(P﹤0.05)。结论 PLGF和TGF-β1可作为预测葡萄胎恶变的参考指标,联合葡萄胎恶变的高危因素,有助于葡萄胎恶变的预测。
Objective To explore the expressions of transforming growth factor beta 1(TGF-β1) and placental growth factor(PLGF) in hydatidiform mole. Method A total of 180 cases of hydatidiform mole were followed for at least 1 year, in which 30 cases developed invasive hydatidiform mole, and 1 was choriocarcinoma. Immunohistochemical method was used to detect the expression levels of TGF-β1 and PLGF in 33 cases with early abortion(control group), 33 cases with non-malignant hydatidiform mole(benign lesions group), and 31 cases with invasive hydatidiform mole(malignant lesions group). Result The positive expression rates of TGF-β1 in invasive hydatidiform mole and choriocarcinoma(58.1%) were significantly lower than that in benign lesions group(87.9%) and control group(97.0%)(P<0.05), while were similar between benign lesions and controls(P>0.05). As for PLGF, the patients with invasive hydatidiform mole and choriocarcinoma had higher positive expression rate(90.3%) than that in control group(36.4%) and benign lesions group(63.6%)(P<0.05), and it was comparable between benign lesions group and control group(P>0.05). Patients with age >40 years, h CG>105U/L, and increased uterine volume had lower TGF-β1 expression(P<0.05) in benign and malignant lesions group; patients with theca lutein cyst diameter >6 cm or recurrent hydatidiform mole had similar positive expression compared with those without the risk factors stated above(P>0.05). In benign and malignant lesions group, patients with age >40 years, h CG>105U/L, and increased uterine volume, or theca lutein cyst diameter >6 cm had higher PLGF expression rate than those without(P<0.05); and those with or without recurrent hydatidiform mole had consistent PLGF levels(P>0.05). There was a negative correlation between TGF-β1 and PLGF expression in patients benign and malignant lesions(P<0.05). Conclusion TGF-β1 and PLGF may become a new index of predicting malignant transformation of hydatidiform mole which provides a basis for preventive chemotherapy.
Objective To explore the expressions of transforming growth factor beta 1(TGF-β1) and placental growth factor(PLGF) in hydatidiform mole. Method A total of 180 cases of hydatidiform mole were followed for at least 1 year, in which 30 cases developed invasive hydatidiform mole, and 1 was choriocarcinoma. Immunohistochemical method was used to detect the expression levels of TGF-β1 and PLGF in 33 cases with early abortion(control group), 33 cases with non-malignant hydatidiform mole(benign lesions group), and 31 cases with invasive hydatidiform mole(malignant lesions group). Result The positive expression rates of TGF-β1 in invasive hydatidiform mole and choriocarcinoma(58.1%) were significantly lower than that in benign lesions group(87.9%) and control group(97.0%)(P<0.05), while were similar between benign lesions and controls(P>0.05). As for PLGF, the patients with invasive hydatidiform mole and choriocarcinoma had higher positive expression rate(90.3%) than that in control group(36.4%) and benign lesions group(63.6%)(P<0.05), and it was comparable between benign lesions group and control group(P>0.05). Patients with age >40 years, h CG>105U/L, and increased uterine volume had lower TGF-β1 expression(P<0.05) in benign and malignant lesions group; patients with theca lutein cyst diameter >6 cm or recurrent hydatidiform mole had similar positive expression compared with those without the risk factors stated above(P>0.05). In benign and malignant lesions group, patients with age >40 years, h CG>105U/L, and increased uterine volume, or theca lutein cyst diameter >6 cm had higher PLGF expression rate than those without(P<0.05); and those with or without recurrent hydatidiform mole had consistent PLGF levels(P>0.05). There was a negative correlation between TGF-β1 and PLGF expression in patients benign and malignant lesions(P<0.05). Conclusion TGF-β1 and PLGF may become a new index of predicting malignant transformation of hydatidiform mole which provides a basis for preventive chemotherapy.
引文
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[15]辛英,温彦静,马天辉,等.子痫前期患者胎盘滋养细胞中TGF-β1与PLGF的表达及相关性[J].中国妇幼保健,2011,26(12):1803-1806.
[2]Liu SC,Xu Q,Yue ZL,et al.Effect of TGF-β1 on TβRⅠ,TβRⅡ,Smad4 m RNA expressions in human choriocarcinoma JEG-3 cell line and the significance[J].Mat Child Health Care China,2015,30(5):758-763.
[3]De Falco S.The discovery of placenta growth factor and its biological activity[J].Exp Mol Med,2012,44(1):1-9.
[4]Bolze PA,Patrier S,Cheynet V,et al.Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles[J].Placenta,2016,39:116-124.
[5]刘绍晨,许倩,岳志领,等.TGF-β1对人绒癌JEG-3细胞株TβRⅠ、TβRⅡ、Smad4 m RNA表达的影响及意义[J].中国妇幼保健,2015,30(5):758-763.
[6]Brooks SA,Martin E,Smeester L,et al.mi RNAs as common regulators of the transforming growth factor(TGF)-βpathway in the preeclamptic placenta and cadmium-treated trophoblasts:Links between the environment,the epigenome and preeclampsia[J].Food Chem Toxicol,2016,98(Pt A):50-57.
[7]Xuan YH,Choi YL,Shin YK,et al.Expression of TGF-beta signaling proteins in normal placenta and gestational trophoblastic disease[J].Histol Histopathol,2007,22(3):227-234.
[8]Cheng JC,Chang HM,Leung PC.Transforming growth factor-β1 inhibits trophoblast cell invasion by inducing Snailmediated down-regulation of vascular endothelial-cadherin protein[J].J Biol Chem,2013,288(46):33181-33192.
[9]Xiang L,Varshney R,Rashdan NA,et al.Placenta growth factor and vascular endothelial growth factor a have differential,cell-type specific patterns of expression in vascular cells[J].Microcirculation,2014,21(5):368-379.
[10]李润花,郑兆祥,武明霞,等.胎盘生长因子及瘦素在早孕绒毛及妊娠滋养细胞疾病中的表达及意义[J].中华妇幼临床医学杂志(电子版),2012,8(4):409-411.
[11]Hussein Y,Snuderl M,Aghajanian C,et al.PIGF/Nrp1/VEGFR1 Axis is upregulated in gestational trophoblastic disease[C]//Laboratory investigation.9th.New York:Nature Publishing Group,2015:291.
[12]Singh M,Kindelberger D,Nagymanyoki Z,et al.Vascular endothelial growth factors and their receptors and regulators in gestational trophoblastic diseases and normal placenta[J].J Reprod Med,2012,57(5-6):197-203.
[13]Okamoto T,Niu R,Mizutani S,et al.Levels of placenta growth factor in gestational trophoblastic diseases[J].Am J Obstet Gynecol,2003,188(1):135-140.
[14]苗向阳.PLGF、TGFβ1和b FGF在膀胱移行细胞癌中的表达及临床意义[D].遵义:遵义医学院,2009.
[15]辛英,温彦静,马天辉,等.子痫前期患者胎盘滋养细胞中TGF-β1与PLGF的表达及相关性[J].中国妇幼保健,2011,26(12):1803-1806.