食管鳞状细胞癌中FOXM1基因的表达及临床意义
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摘要
目的探讨FOXM1基因在食管鳞状细胞癌中的表达和临床意义以及下调FOXM1表达对人食管鳞状细胞癌细胞株KYSE-30增殖活性的影响。方法采用qRT-PCR及免疫组化技术检测FOXM1基因在食管鳞状细胞癌及癌旁组织中的表达;通过RNA干扰技术(RNAi)下调KYSE-30细胞FOXM1表达,CCK-8法检测细胞的增殖活性。结果 qRT-PCR结果显示,食管鳞状细胞癌中FOXM1 mRNA表达显著高于对应癌旁组织(P<0.01);FOXM1 mRNA在低分化食管鳞状细胞癌组织中的表达量显著高于高+中分化食管鳞状细胞癌组织(P<0.01);FOXM1 mRNA过表达与食管鳞状细胞癌肿瘤分化程度(P=0.001)、淋巴结转移(P=0.000)、临床分期(P=0.004)显著相关;高表达FOXM1食管鳞状细胞癌患者生存率下降(P<0.001)。免疫组化结果显示,FOXM1蛋白在食管鳞状细胞癌中的表达显著增高并与其分化程度密切相关(P<0.01);下调KYSE-30细胞中FOXM1表达后,细胞增殖速度受抑制(P<0.01)。结论 FOXM1在食管鳞状细胞癌组织中呈高表达,并与食管癌分化程度、淋巴结转移、临床分期及预后密切相关,FOXM1可能参与调控人食管鳞状细胞癌细胞KYSE-30的增殖。
Purpose Analysis of correlation between FOXM1 gene expression levels and clinicopathological featuresand prognosis of patients with esophageal squamous cancer(ESC).The effect of down-regulation of FOXM1 expression on the proliferation of human ESC cell line KYSE-30 was also investigated.Methods Quantitative real-time PCR(qRT-PCR) and immunohistochemistry(IHC) methods were used to detect the expression of FOXM1 in ESC tissues and non-cancer tissues in mRNA and protein level.The expression of FOXM1 was downregulated by RNA interference(RNAi) technique,and the proliferation activity of KYSE-30 cells was detected by CCK-8 assay.Results Compared with the corresponding non-cancer tissues,the expression of FOXM1 was significant higher in ESC tissues(P < 0.01).Meanwhile,the expression levels of FOXM1 in poorly differentiated esophageal carcinoma was higher than that in well-differentiated ESC group(P < 0.01).The expression ofFOXM1 was significantly correlated with poor tumor differentiation(P < 0.001),lymphatic metastasis(P = 0.000),advanced stage(P = 0.004) of ESC patients after surgical resection.High FOXM1 expression was related to shorter overall survival(OS)(P < 0.001).After down-regulating FOXM1 expression in KYSE-30 cells,cell proliferation rate was inhibited(P < 0.01).Conclusion FOXM1 expression is up-regulated in ESC and is closely related to the degree of differentiation,lymph node metastasis,clinical stage and prognosis of ESC.FOXM1 may be participated in regulating the proliferation of human esophageal carcinoma cell line KYSE-30.
Purpose Analysis of correlation between FOXM1 gene expression levels and clinicopathological featuresand prognosis of patients with esophageal squamous cancer(ESC).The effect of down-regulation of FOXM1 expression on the proliferation of human ESC cell line KYSE-30 was also investigated.Methods Quantitative real-time PCR(qRT-PCR) and immunohistochemistry(IHC) methods were used to detect the expression of FOXM1 in ESC tissues and non-cancer tissues in mRNA and protein level.The expression of FOXM1 was downregulated by RNA interference(RNAi) technique,and the proliferation activity of KYSE-30 cells was detected by CCK-8 assay.Results Compared with the corresponding non-cancer tissues,the expression of FOXM1 was significant higher in ESC tissues(P < 0.01).Meanwhile,the expression levels of FOXM1 in poorly differentiated esophageal carcinoma was higher than that in well-differentiated ESC group(P < 0.01).The expression ofFOXM1 was significantly correlated with poor tumor differentiation(P < 0.001),lymphatic metastasis(P = 0.000),advanced stage(P = 0.004) of ESC patients after surgical resection.High FOXM1 expression was related to shorter overall survival(OS)(P < 0.001).After down-regulating FOXM1 expression in KYSE-30 cells,cell proliferation rate was inhibited(P < 0.01).Conclusion FOXM1 expression is up-regulated in ESC and is closely related to the degree of differentiation,lymph node metastasis,clinical stage and prognosis of ESC.FOXM1 may be participated in regulating the proliferation of human esophageal carcinoma cell line KYSE-30.
引文
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[13]Yang L,Cui M,Zhang L,et al.FOXM1 facilitates gastric cancer cell migration and invasion by inducing Cathepsin D[J].Oncotarget,2017,8(37):61499-61509.
[14]Zhou Y,Ji Z,Yan W L,et al.Tetramethylpyrazine inhibits prostate cancer progression by downregulation of forkhead box M1[J].Oncol Rep,2017,38(2):837-842.
[15]Okato A,Arai T,Yamada Y,et al.Dual strands of Pre-miR-149inhibit cancer cell migration and invasion through targeting FOXM1in renal cell carcinoma[J].Int J Mol Sci,2017,18(9):648-655.
[2]王道猛,钱斌,吴俊,等.胸腹腔镜联合治疗食管癌的临床价值[J].中华消化外科杂志,2015,14(12):1012-1015.
[3]赫捷,邵康.中国食管癌流行病学现状、诊疗现状及未来对策[J].中国癌症杂志,2011,21(7):501-504.
[4]井贺楠,李静雅,许芝山,等.CD137/CD137L在食管癌中表达与预后的相关性分析[J].中国医药导报,2017,14(2):4-7,24.
[5]韦林,任松,朱昌生,等.食管癌中NEDD9的表达与预后[J].现代肿瘤医学,2016,24(14):2011-2013.
[6]Wierstra I,Alves J.FOXM1,a typical proliferation-associated transcriptionfactor[J].Biol Chem,2007,388(12):1257-1274.
[7]Laoukili J,Kooistra M R,Bras A,et al.Fox M1 is required for execution of the mitotic programme and chromosome stability[J].Nat Cell Biol,2005,7(2):126-136.
[8]Li M,Yang J,Zhou W,et al.Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer[J].Br J Cancer,2017,117(7):974-983.
[9]朱霞,鲁康洋,江燕,等.foxm1抑制剂下调Rad51增敏顺铂对骨肉瘤耐药细胞的化疗抑制作用[J].临床与实验病理学杂志,2017,33(4):403-407.
[10]Obama K,Ura K,Li M,et al.Genome-wide analysis of gene expression in human intrahepatic cholangiocareinoma[J].Hepatology,2005,41(6):1339-1348.
[11]陆明,胡孔旺,王宜文,等.叉头框M1在结直肠癌中的表达及临床意义[J].临床与实验病理学杂志,2017,33(8):847-852.
[12]Wang J M,Ju B H,Pan C J,et al.MiR-214 inhibits cell migration,invasion and promotes the drug sensitivity in human cervical cancerby targeting FOXM1[J].Am J Transl Res,2017,9(8):3541-3557.
[13]Yang L,Cui M,Zhang L,et al.FOXM1 facilitates gastric cancer cell migration and invasion by inducing Cathepsin D[J].Oncotarget,2017,8(37):61499-61509.
[14]Zhou Y,Ji Z,Yan W L,et al.Tetramethylpyrazine inhibits prostate cancer progression by downregulation of forkhead box M1[J].Oncol Rep,2017,38(2):837-842.
[15]Okato A,Arai T,Yamada Y,et al.Dual strands of Pre-miR-149inhibit cancer cell migration and invasion through targeting FOXM1in renal cell carcinoma[J].Int J Mol Sci,2017,18(9):648-655.