Zhao F, Yu X P, Zhao H, Song B B, Lyu A W, Zhang S H, Wang L M
Department of Gynecology, Qingdao University Affiliated Hospital, Qingdao 266003, China.
Department of Gynecology, Shandong Weihai Women's and Children's Hospital, Weihai 264299, China.
Zhonghua Fu Chan Ke Za Zhi. 2022 Feb 25;57(2):125-132. doi: 10.3760/cma.j.cn112141-20211219-00736.
To investigate the expression levels and clinical significance of glioma-associated oncogene homolog 1 (GLI1) and sonic hedgehog signaling molecule (Shh) in the malignant transformation of ovarian endometriosis (EM). The expressions of GLI1 and Shh were detected by real-time reverse transcription (RT)-polymerase chain reaction (PCR) and EnVision method in 50 cases of ovarian EM tissues, 35 cases of atypical endometriosis (aEM) and 50 cases of endometriosis-associated ovarian cancer (EAOC). The expression differences of two molecular markers in the malignant transformation of ovarian EM were compared, and the relationships between two molecular markers and the clinicopathological features and prognosis of EAOC were analyzed. (1) RT-PCR showed that the expression levels of GLI1 mRNA in EM, aEM and EAOC group were 1.77±0.40, 3.54±0.44, and 7.80±0.24, respectively. The expression levels of Shh mRNA were 0.95±0.21, 3.14±0.35, and 5.41±0.31, respectively. GLI1 and Shh mRNA in EAOC group were significantly higher than those in EM and aEM group (all <0.01), and there were statistically significant differences between EM and aEM group (all <0.01). The percentages of GLI1 in ovarian EM, aEM and EAOC were 32% (16/50), 57% (20/35), and 66% (33/50), respectively, meanwhile, the positive expression rates of Shh were 20% (10/50), 49% (17/35), and 54% (27/50), respectively (all <0.01). GLI1 mRNA expression was positively correlated with Shh mRNA expression in EAOC tissues (=0.721, <0.01). The expressions of GLI1 protein were proportionated to Shh protein in EAOC tissues (=0.608,=0.001). (2) The expression of GLI1 was significantly related to the International Federation of Gynecology and Obstetrics (FIGO) stage, cancer antigen 125 (CA) levels, lymph node metastasis, and Platinum resistance in EAOC patients (all <0.05). The expression of Shh were related to FIGO stage and lymph node metastasis in EAOC patients (all <0.05). Logistic regression analysis showed that GLI1 expression was an independent risk factor for poor prognosis in EAOC patients (<0.05). Kaplan-meier survival analysis showed that the overall survival rate of EAOC patients with high GLI1 expression and low GLI1 expression was 12.1% and 35.3%, respectively, with statistical significance (²=10.73, <0.01). The overall survival rate of EAOC patients with high and low expression of Shh protein was 11.1% and 30.4%, in which there was statistically significant difference (²=3.96, =0.047). GLI1 and Shh are highly associated with the malignant transformation of ovarian EM, which may play a role in promoting malignant degeneration of ovarian EM, and the high expression of GLI1 and Shh indicates a poor prognosis in EAOC patients.
探讨胶质瘤相关癌基因同源物1（GLI1）和音猬因子信号分子（Shh）在卵巢子宫内膜异位症（EM）恶变中的表达水平及临床意义。采用实时逆转录（RT）-聚合酶链反应（PCR）和EnVision法检测50例卵巢EM组织、35例不典型子宫内膜异位症（aEM）及50例子宫内膜异位症相关卵巢癌（EAOC）中GLI1和Shh的表达。比较两种分子标志物在卵巢EM恶变中的表达差异，并分析其与EAOC临床病理特征及预后的关系。（1）RT-PCR结果显示，EM组、aEM组及EAOC组GLI1 mRNA表达水平分别为1.77±0.40、3.54±0.44及7.80±0.24。Shh mRNA表达水平分别为0.95±0.21、3.14±0.35及5.41±0.31。EAOC组GLI1和Shh mRNA表达均显著高于EM组及aEM组（均P<0.01），EM组与aEM组比较差异也有统计学意义（均P<0.01）。卵巢EM、aEM及EAOC中GLI1阳性率分别为32%（16/50）、57%（20/35）及66%（33/50），Shh阳性表达率分别为20%（10/50）、49%（17/35）及54%（27/50）（均P<0.01）。EAOC组织中GLI1 mRNA表达与Shh mRNA表达呈正相关（r=0.721，P<0.01）。EAOC组织中GLI1蛋白表达与Shh蛋白表达成比例（r=0.608，P=0.001）。（2）EAOC患者中GLI1表达与国际妇产科联盟（FIGO）分期、癌抗原125（CA）水平、淋巴结转移及铂耐药均显著相关（均P<0.05）。Shh表达与EAOC患者FIGO分期及淋巴结转移相关（均P<0.05）。Logistic回归分析显示，GLI1表达是EAOC患者预后不良的独立危险因素（P<0.05）。Kaplan-Meier生存分析显示，GLI1高表达与低表达的EAOC患者总生存率分别为12.1%和35.3%，差异有统计学意义（χ²=10.73，P<0.01）。Shh蛋白高表达与低表达的EAOC患者总生存率分别为11.1%和30.4%，差异有统计学意义（χ²=3.96，P=0.047）。GLI1和Shh与卵巢EM恶变高度相关，可能在促进卵巢EM恶变中起作用，且GLI1和Shh高表达提示EAOC患者预后不良。
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