上皮性卵巢癌中ERCC1及转录因子Nanog蛋白的表达水平及意义

Expression levels of ERCC1 and transcription factor Nanog protein in epithelial ovarian cancer and their significance

摘要

目的 探讨上皮性卵巢癌中核昔酸切除修复交叉互补组1(ERCC1)及转录因子Nanog蛋白的表达水平及意义。方法 收集2019年1月至2022年12月在连云港市肿瘤医院妇科行卵巢手术切除的组织标本,其中上皮性卵巢癌组织标本101例(上皮性卵巢癌组),良性卵巢肿瘤组织标本80例(对照组),采用免疫组化检测ERCC1及Nanog蛋白表达水平,并分析与临床病理指标的关系.分别用0mg/L、1mg/L、2mg/L、4mg/L不同浓度的顺铂处理人卵巢癌OVCAR-3细胞24h,以Western blot检测细胞中ERCC1、Nanog蛋白的相对表达量,比较两组间ERCC1及Nanog蛋白的表达水平。结果 上皮性卵巢癌组ERCC1、Nanog蛋白的阳性率均明显高于对照组,差异均有统计学意义(χ²值分别为49.960、39.941,P＜0.05).Spearman相关性分析显示,上皮性卵巢癌组中ERCC1与Nanog蛋白表达水平呈正相关(r＝0.463,P＜0.01);对照组中ERCC1与Nanog蛋白表达水平无相关性(r＝0.125,P＞0.05).在上皮性卵巢癌临床病理指标中,FIGO分期为Ⅲ＋Ⅳ期的ERCC1、Nanog蛋白的阳性率均明显高于Ⅰ＋Ⅱ期(χ²值分别为9.578、9.756),淋巴结转移阳性的ERCC1、Nanog蛋白阳性率均明显高于淋巴结转移阴性(χ²值分别为3.018、2.389),经比较差异均有统计学意义(P＜0.05).1mg/L、2mg/L、4mg/L浓度顺铂处理的ERCC1和Nanog蛋白相对表达量均明显高于0mg/L浓度顺铂处理的相对表达量,经比较差异均有统计学意义(F值分别为8.564、6.571,P＜0.05);在ERCC1、Nanog蛋白相对表达量中,顺铂处理浓度1mg/L与0mg/L相比(t值分别为17.236、5.381)、顺铂处理浓度2mg/L与0mg/L相比(t值分别为5.621、6.380)、顺铂处理浓度4mg/L与0mg/L相比(t值分别为12.813、6.810),差异均有统计学意义(P＜0.05);且随顺铂浓度的增加,ERCC1、Nanog蛋白相对表达量逐渐升高。结论 ERCC1及Nanog蛋白在上皮性卵巢癌中呈现出高表达,可能与该病的发病机理和病情发展具有相关性.顺铂可诱导卵巢癌细胞ERCC1及Nanog蛋白高表达,可能为化疗耐药的潜在机制.

Abstract

Objective To explore expression levels and significance of ERCC1 and transcription factor Nanog protein in epithelial ovarian cancer. Methods 181 tissue specimens of patients who underwent ovarian surgery in Lianyungang Municipal Cancer Hospital from January 2019 to December 2022 were collected, including 101 specimens of epithelial ovarian cancer (epithelial ovarian cancer group) and 80 specimens of benign ovarian tumors (control group). Immunohistochemistry was used to detect expression levels of ERCC1 and Nanog protein, and their relationships with clinicopathological indexes were analyzed. OVCAR-3 cells were treated with different concentrations (0mg/L, 1mg/L, 2mg/L and 4mg/L) of cisplatin for 24 hours, and Western blot method was used to detect relative expression levels of ERCC1 and Nanog protein in the cells. The differences in expression levels of ERCC1 and Nanog protein between the two groups were compared. Results The positive expression rates of ERCC1 and Nanog protein in the epithelial ovarian cancer group were significantly higher than those in the control group, and the differences were statistically significant (t＝49.960 and 39.941 respectively, both P＜0.05). Spearman correlation analysis showed that in the epithelial ovarian cancer group, the expression level of ERCC1 was positively correlated with that of Nanog protein (r＝0.463, P＜0.01); while there was no correlation between the expression level of ERCC1 and the expression level of Nanog protein in the control group (r＝0.125, P＞0.05). The positive rates of ERCC1 and Nanog protein in these ovarian cancer tissues with FIGO stage Ⅲ＋Ⅳ were significantly higher than those in those ovarian cancer tissues with FIGO stage Ⅰ＋Ⅱ (χ ²＝9.578 and 9.756 respectively), and the positive rates of ERCC1 and Nanog protein in these ovarian cancer tissues with positive lymph node metastasis were significantly higher than those in those ovarian cancer tissues without lymph node metastasis (χ²＝3.018 and 2.389 respectively), and the differences were statistically significant (all P＜0.05). After 24 hours of treatment with different concentrations of cisplatin on OVCAR-3 cells, the relative expression levels of ERCC1 and Nanog protein in the 1mg/L, 2mg/L and 4mg/L of cisplatin treated OVCAR-3 cells groups were significantly higher than those in the 0mg/L of cisplatin treated OVCAR-3 cells group, and the differences were statistically significant (F＝8.564 and 6.571 respectively, both P＜0.05). In the relative expression amounts of ERCC1 and Nanog protein, there were significant differences between the 1mg/L of cisplatin treated OVCAR-3 cells group and 0mg/L of cisplatin treated OVCAR-3 cells group (t＝17.236 and 5.381 respectively), between the 2mg/L of cisplatin treated OVCAR-3 cells group and 0mg/L of cisplatin treated OVCAR-3 cells group (t＝5.621 and 6.380 respectively), and between the 4mg/L of cisplatin treated OVCAR-3 cells group and 0mg/L of cisplatin treated OVCAR-3 cells group (t＝12.813 and 6.810 respectively), and the differences were statistically significant (all P＜0.05). And with increase in cisplatin concentration, the relative expression amounts of ERCC1 and Nanog protein gradually increased. Conclusion ERCC1 and Nanog are highly expressed in epithelial ovarian cancer, which may be related to the pathogenesis and the progression of the disease. Cisplatin can induce high expressions of ERCC1 and Nanog protein in ovarian cancer cells, which may be a potential mechanism of chemotherapy resistance.

关键词

上皮性卵巢癌 / 核昔酸切除修复交叉互补组1 / Nanog蛋白 / 耐药性

Key words

epithelial ovarian cancer / nucleotide excision repair cross complementation group 1 / Nanog protein / drug resistance

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