子宫内膜癌组织Fat-1基因表达的变化及其对癌细胞生长的调控作用研究
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摘要
目的:研究子宫内膜癌中Fat-1基因表达的变化及其对癌细胞生长的调控作用。方法:选择2016年8月~2017年8月期间在西京医院接受手术切除治疗的150例子宫内膜癌患者作为研究的恶性组,并收集子宫内膜癌组织,另取同期在西京医院接受子宫全切除术的80例良性病变患者作为研究的对照组,并收集正常子宫内膜组织,检测Fat-1基因、抑癌基因、增殖基因、血管新生基因的mRNA表达量。结果:恶性组子宫内膜癌组织中Fat-1、PTEN、p16、BRCA1、Bid、Caspase-3的mRNA表达量均显著低于对照组,恶性组子宫内膜癌组织中SRPX2、TET1、CyclinD1、HMGB1、Livin、Septin9、β-arrestin2、HIF-1α、VEGF的mRNA表达量均显著高于对照组;Pearson分析显示:子宫内膜癌组织中Fat-1的mRNA表达量与PTEN、p16、BRCA1、Bid、Caspase-3的mRNA表达量呈正相关,与SRPX2、TET1、CyclinD1、HMGB1、Livin、Septin9、β-arrestin2、HIF-1α、VEGF的mRNA表达量呈负相关。结论:子宫内膜癌中Fat-1基因的低表达对癌细胞的生长具有促进作用。
Objective:To study the change of Fat-1 gene expression and its regulating effect on the growth of cancer cells in endometrial cancer.Methods:A total of 150 patients with endometrial cancer who underwent surgical resection in Xijing Hospital between August 2016 and August 2017 were selected as the malignant group of the study to collect the endometrial cancer tissues,80 patients with benign lesions who underwent total hysterectomy in Xijing Hospital during the same period were selected as the control group of the study to collect normal endometrial tissues,and the mRNA expression levels of Fat-1 gene,tumor suppressor genes,proliferation genes and angiogenesis genes were determined.Results:Fat-1,PTEN,p16,BRCA1,Bid and Caspase-3 mRNA expression in endometrial cancer tissues of malignant group were significantly lower than those of control group whereas SRPX2,TET1,CyclinD1,HMGB1,Livin,Septin9,β-arrestin2,HIF-1αand VEGF mRNA expression in endometrial cancer tissues of malignant group were significantly higher than those of control group(P<0.05);Pearson analysis showed that Fat-1 mRNA expression in endometrial cancer tissues was positively correlated with PTEN,p16,BRCA1,Bid and Caspase-3 mRNA expression,and negatively correlated with SRPX2,TET1,CyclinD1,HMGB1,Livin,Septin9,β-arrestin2,HIF-1αand VEGF mRNA expression.Conclusion:The low expression of Fat-1 gene in endometrial cancer promotes the growth of cancer cells.
Objective:To study the change of Fat-1 gene expression and its regulating effect on the growth of cancer cells in endometrial cancer.Methods:A total of 150 patients with endometrial cancer who underwent surgical resection in Xijing Hospital between August 2016 and August 2017 were selected as the malignant group of the study to collect the endometrial cancer tissues,80 patients with benign lesions who underwent total hysterectomy in Xijing Hospital during the same period were selected as the control group of the study to collect normal endometrial tissues,and the mRNA expression levels of Fat-1 gene,tumor suppressor genes,proliferation genes and angiogenesis genes were determined.Results:Fat-1,PTEN,p16,BRCA1,Bid and Caspase-3 mRNA expression in endometrial cancer tissues of malignant group were significantly lower than those of control group whereas SRPX2,TET1,CyclinD1,HMGB1,Livin,Septin9,β-arrestin2,HIF-1αand VEGF mRNA expression in endometrial cancer tissues of malignant group were significantly higher than those of control group(P<0.05);Pearson analysis showed that Fat-1 mRNA expression in endometrial cancer tissues was positively correlated with PTEN,p16,BRCA1,Bid and Caspase-3 mRNA expression,and negatively correlated with SRPX2,TET1,CyclinD1,HMGB1,Livin,Septin9,β-arrestin2,HIF-1αand VEGF mRNA expression.Conclusion:The low expression of Fat-1 gene in endometrial cancer promotes the growth of cancer cells.
引文
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4 Yum HW,Park J,Park HJ,et al.Endogenousω-3fatty acid production by fat-1transgene and topically applied docosahexaenoic acid protect against UVB-induced mouse skin carcinogenesis[J].Sci Rep,2017,7(1):11658.
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6 Geletina NS,Kobelev VS,Babayants EV,et al.PTEN negative correlates with miR-181ain tumour tissues of non-obese endometrial cancer patients[J].Gene,2018,20(655):20-24.
7 Li W,Wang Y,Fang X,et al.Differential expression and clinical significance of DNA methyltransferase 3B(DNMT3B),phosphatase and tensin homolog(PTEN)and human mutl homologs 1(hMLH1)in endometrial carcinomas[J].Med Sci Monit,2017,21(23):938-947.
8 Yoon G,Koh CW,Yoon N,et al.Stromal p16expression is significantly increased in endometrial carcinoma[J].Oncotarget,2017,8(3):4826-4836.
9 Driak D,Dvorska M,Bolehovska P,et al.Bad and Bid-potential background players in preneoplastic to neoplastic shift in human endometrium[J].Neoplasma,2014,61(4):411-415.
10 Lv QY,Xie BY,Yang BY,et al.Increased TET1Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER[J].J Cancer,2017,8(5):894-902.
11 Stewart CJ,Crook ML.PAX2and cyclin D1expression in the distinction between cervical microglandular hyperplasia and endometrial microglandular-like carcinoma:a comparison with p16,vimentin,and Ki67[J].Int J Gynecol Pathol,2015,34(1):90-100.
12 Luan X,Ma C,Wang P,et al.HMGB1is negatively correlated with the development of endometrial carcinoma and prevents cancer cell invasion and metastasis by inhibiting the process of epithelial-to-mesenchymal transition[J].Onco Targets Ther,2017,3(10):1389-1402.
13 Connolly D,Hoang HG,Adler E,et al.Septin 9amplification and isoform-specific expression in peritumoral and tumor breast tissue[J].Biol Chem,2014,395(2):157-167.
14 Al-Sharaky DR,Abdou AG,Wahed MM,et al.HIF-1 αand GLUT-1expression in atypical endometrial hyperplasia,type I andⅡendometrial carcinoma:A potential role in pathogenesis[J].J Clin Diagn Res,2016,10(5):20-27.
15 Sun X,Zhang Y,Wang J,et al.Beta-arrestin 2modulates resveratrol-induced apoptosis and regulation of Akt/GSK3βpathways[J].Biochim Biophys Acta,2010,1800(9):912-918.
16 Xu H,Sun X,Sun WJ.Expression and clinical correlation of NGAL and VEGF in endometrial carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(3):632-636.
17 Mahecha AM,Wang H.The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2and-9in angiogenesis,metastasis,and prognosis of endometrial cancer[J].Onco Targets Ther,2017,19(10):4617-4624.
2 Rouzbahman M.Diagnosis of neoplasia in endometrial biopsies:A pattern-based and algorithmic approach[J].J Clin Pathol,2016,69(2):185.
3 梁升,陆晓媛.Fat-1基因对人子宫内膜癌Ishikawa细胞体内生长抑制作用[J].现代妇产科进展,2017,26(5):333-336.
4 Yum HW,Park J,Park HJ,et al.Endogenousω-3fatty acid production by fat-1transgene and topically applied docosahexaenoic acid protect against UVB-induced mouse skin carcinogenesis[J].Sci Rep,2017,7(1):11658.
5 Yum HW,Kang JX,Hahm KB,et al.Constitutiveω-3fatty acid production in fat-1transgenic mice and docosahexaenoic acid administration to wild type mice protect against 2,4,6-trinitrobenzene sulfonic acid-induced colitis[J].Biochem Biophys Res Commun,2017,487(4):847-855.
6 Geletina NS,Kobelev VS,Babayants EV,et al.PTEN negative correlates with miR-181ain tumour tissues of non-obese endometrial cancer patients[J].Gene,2018,20(655):20-24.
7 Li W,Wang Y,Fang X,et al.Differential expression and clinical significance of DNA methyltransferase 3B(DNMT3B),phosphatase and tensin homolog(PTEN)and human mutl homologs 1(hMLH1)in endometrial carcinomas[J].Med Sci Monit,2017,21(23):938-947.
8 Yoon G,Koh CW,Yoon N,et al.Stromal p16expression is significantly increased in endometrial carcinoma[J].Oncotarget,2017,8(3):4826-4836.
9 Driak D,Dvorska M,Bolehovska P,et al.Bad and Bid-potential background players in preneoplastic to neoplastic shift in human endometrium[J].Neoplasma,2014,61(4):411-415.
10 Lv QY,Xie BY,Yang BY,et al.Increased TET1Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER[J].J Cancer,2017,8(5):894-902.
11 Stewart CJ,Crook ML.PAX2and cyclin D1expression in the distinction between cervical microglandular hyperplasia and endometrial microglandular-like carcinoma:a comparison with p16,vimentin,and Ki67[J].Int J Gynecol Pathol,2015,34(1):90-100.
12 Luan X,Ma C,Wang P,et al.HMGB1is negatively correlated with the development of endometrial carcinoma and prevents cancer cell invasion and metastasis by inhibiting the process of epithelial-to-mesenchymal transition[J].Onco Targets Ther,2017,3(10):1389-1402.
13 Connolly D,Hoang HG,Adler E,et al.Septin 9amplification and isoform-specific expression in peritumoral and tumor breast tissue[J].Biol Chem,2014,395(2):157-167.
14 Al-Sharaky DR,Abdou AG,Wahed MM,et al.HIF-1 αand GLUT-1expression in atypical endometrial hyperplasia,type I andⅡendometrial carcinoma:A potential role in pathogenesis[J].J Clin Diagn Res,2016,10(5):20-27.
15 Sun X,Zhang Y,Wang J,et al.Beta-arrestin 2modulates resveratrol-induced apoptosis and regulation of Akt/GSK3βpathways[J].Biochim Biophys Acta,2010,1800(9):912-918.
16 Xu H,Sun X,Sun WJ.Expression and clinical correlation of NGAL and VEGF in endometrial carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(3):632-636.
17 Mahecha AM,Wang H.The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2and-9in angiogenesis,metastasis,and prognosis of endometrial cancer[J].Onco Targets Ther,2017,19(10):4617-4624.