叉头框蛋白Q1在宫颈鳞癌中的表达及其临床意义
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摘要
目的:探讨叉头框蛋白Q1(forkhead box Q1,FOXQ1)在宫颈鳞癌细胞系及组织中的表达及其与患者临床病理特征和预后的关系。方法:采用RT-PCR和Western blot检测宫颈鳞癌细胞系SiHa和CaSki及人宫颈永生化鳞状细胞系Ect1/E6E7中FOXQ1 mRNA和蛋白的表达情况;分别应用RT-PCR及免疫组化法检测60例宫颈鳞癌组织中FOXQ1 mRNA和蛋白的表达情况;进一步采用Log-rank检验和Cox回归模型对宫颈鳞癌患者的预后因素进行分析,并用Kaplan-Meier计算不同FOXQ1表达情况下患者的生存率曲线。结果:与Ect1/E6E7相比,SiHa和CaSki中FOXQ1 mRNA和蛋白的表达水平均显著上调(P <0. 05);宫颈鳞癌组织中FOXQ1 mRNA的表达水平显著高于配对癌旁组织(3. 096±0. 109 vs 0. 902±0. 040,P <0. 01);免疫组化结果显示,FOXQ1蛋白在宫颈鳞癌组织中高表达,阳性率为68. 33%,且FOXQ1蛋白的表达与肿瘤浸润深度、淋巴结转移、淋巴脉管浸润及FIGO分期有关(P <0. 05),而与患者的年龄、肿瘤分化程度和肿瘤大小无关(P <0. 05); Kaplan-Meier单因素分析显示,FOXQ1蛋白是宫颈鳞癌患者的重要预后因素(P <0. 05),进一步Cox多因素回归分析显示FOXQ1蛋白是影响宫颈鳞癌患者的独立预后因素(HR=2. 703,95%CI:1. 081～6. 758,P <0. 05)。结论:FOXQ1的高表达可能与宫颈鳞癌的发生、发展及预后关系密切,有望成为评估宫颈鳞癌预后的有效指标。
Objective: To investigate the expression of forkhead box Q1( FOXQ1) in cervical squamous cell carcinoma cell lines and tissues and its relationship with clinicopathological characteristics and prognosis. Methods:FOXQ1 mRNA and protein expression in human cervical squamous cell carcinoma cell lines( Si Ha and Ca Ski) and human cervical immortalized squamous cell line( Ect1/E6 E7) were detected by RT-PCR and Western blot,respectively. The FOXQ1 mRNA and protein expression in 60 cervical squamous cell carcinoma tissues and paired adjacent tissues were investigated by RT-PCR and immunohistochemistry method,respectively. Kaplan-Meier survival curves,Log-rank test and Cox multivariate test regression were used to analyze the clinicopathological prognostic factors of gastric cancer. Results: The mRNA and protein expression of FOXQ1 in both Si Ha and Ca Ski were higher than Ect1/E6 E7( P < 0. 05,respectively). FOXQ1 was discovered highly expressed at mRNA levels in the cervical squamous cell carcinoma tissue samples compared with the paired adjacent tissues( 3. 096 ± 0. 109 vs 0. 902 ± 0. 040,P< 0. 01). Furthermore,the results of immunohistochemistry showed that FOXQ1 protein was highly expressed in cervical squamous cell carcinoma tissues with a positive rate of 68. 33%,and the expression of FOXQ1 protein was related to tumor infiltration depth,lymph node metastasis,lymphovascular invasion and FIGO stage( P < 0. 05,respectively),but not with the patient's age,histological grade and tumor size( P > 0. 05,respectively). Kaplan-Meier univariate analysis showed that FOXQ1 protein was an important factor for affecting the prognosis of cervical squamous cell carcinoma( P < 0. 05),and further Cox regression analysis demonstrated that FOXQ1 protein was an independent prognostic risk factor of cervical squamous cell carcinoma cancer( HR = 2. 703,95% CI: 1. 081 ～ 6. 758,P < 0. 05). Conclusion: The high expression of FOXQ1 may be closely related to the occurrence,development and prognosis of cervical squamous cell carcinoma,and it may be an effective indicator to evaluate the prognosis of cervical squamous cell carcinoma.
Objective: To investigate the expression of forkhead box Q1( FOXQ1) in cervical squamous cell carcinoma cell lines and tissues and its relationship with clinicopathological characteristics and prognosis. Methods:FOXQ1 mRNA and protein expression in human cervical squamous cell carcinoma cell lines( Si Ha and Ca Ski) and human cervical immortalized squamous cell line( Ect1/E6 E7) were detected by RT-PCR and Western blot,respectively. The FOXQ1 mRNA and protein expression in 60 cervical squamous cell carcinoma tissues and paired adjacent tissues were investigated by RT-PCR and immunohistochemistry method,respectively. Kaplan-Meier survival curves,Log-rank test and Cox multivariate test regression were used to analyze the clinicopathological prognostic factors of gastric cancer. Results: The mRNA and protein expression of FOXQ1 in both Si Ha and Ca Ski were higher than Ect1/E6 E7( P < 0. 05,respectively). FOXQ1 was discovered highly expressed at mRNA levels in the cervical squamous cell carcinoma tissue samples compared with the paired adjacent tissues( 3. 096 ± 0. 109 vs 0. 902 ± 0. 040,P< 0. 01). Furthermore,the results of immunohistochemistry showed that FOXQ1 protein was highly expressed in cervical squamous cell carcinoma tissues with a positive rate of 68. 33%,and the expression of FOXQ1 protein was related to tumor infiltration depth,lymph node metastasis,lymphovascular invasion and FIGO stage( P < 0. 05,respectively),but not with the patient's age,histological grade and tumor size( P > 0. 05,respectively). Kaplan-Meier univariate analysis showed that FOXQ1 protein was an important factor for affecting the prognosis of cervical squamous cell carcinoma( P < 0. 05),and further Cox regression analysis demonstrated that FOXQ1 protein was an independent prognostic risk factor of cervical squamous cell carcinoma cancer( HR = 2. 703,95% CI: 1. 081 ～ 6. 758,P < 0. 05). Conclusion: The high expression of FOXQ1 may be closely related to the occurrence,development and prognosis of cervical squamous cell carcinoma,and it may be an effective indicator to evaluate the prognosis of cervical squamous cell carcinoma.
引文
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[21]LIU Huifang,CAO Mengting,XU Wei,et al.The transcription factors and their related signaling pathways in the regulation of tumor EMT[J].Modern Oncology,2017,25(13):2155-2160.[刘卉芳,曹梦婷,徐薇,等.调控肿瘤EMT的转录因子及其相关信号通路[J].现代肿瘤医学,2017,25(13):2155-2160.]
[22]Feng J,Xu L,Ni S,et al.Involvement of Fox Q1 in NSCLC through regulating EMT and increasing chemosensitivity[J].Oncotarget,2014,5(20):9689-9702.
[2]Lamouille S,Xu J,Derynck R.Molecular mechanisms of epithelial-mesenchymal transition[J].Nat Rev Mol Cell Biol,2014,15(3):178-196.
[3]ZHAO FP,LIANG ZP,PENG XH,et al.Expression of forkhead box Q1 in nasopharyngeal carcinoma tissue and its clinical significance[J].Journal of Sowthwest Medical University,2017,40(4):402-406.[赵飞鹏,梁灼萍,彭小红,等.鼻咽癌组织中FOXQ1的表达及其临床意义[J].西南医科大学学报,2017,40(4):402-406.]
[4]WANG B,ZHANG X,GENG H,et al.Expression and relationship between forkhead box Q1 and prognosis in NSCLC[J].Chongqing Medicine,2015,44(1):63-65.[王斌,张逊,耿华,等.叉头框蛋白Q1在非小细胞肺癌的表达及其与预后关系[J].重庆医学,2015,44(1):63-65.]
[5]YAO NH,GAI L,HUANG H,et al.Expression and prognosis of Fox Q1 in esophageal squamous cell carcinoma[J].International Journal of Pathology and Clinical Medicine,2015,35(9):1632-1636.[姚宁华,盖领,黄华,等.Fox Q1在食管鳞状细胞癌中的表达及其与预后[J].临床与病理杂志,2015,35(9):1632-1636.]
[6]LIANG SH,YAN XZ,WANG BL,et al.Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer[J].Tumour Biol,2013,34(5):2605-2609.
[7]GUO YP,ZHOU J,LUAN YY,et al.FOXQ1 expression in high and low grade serous ovarian carcinoma and its relationship with lymph node metastasis and long-term survival rate[J].Shanxi Medical Journal,2017,46(4):381-384.[郭艳萍,周巾,栾媛媛,等.FOXQ1在卵巢高低级别浆液性癌中的阳性表达与淋巴结转移及其远期生存率的关系[J].山西医药杂志,2017,46(4):381-384.]
[8]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[9]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[10]Kumar L,Harish P,Malik PS,et al.Chemotherapy and targeted therapy in the management of cervical cancer[J].Curr Probl Cancer,2018,42(2):120-128.
[11]Katoh M,Katoh M.Human FOX gene family(review)[J].Int JOncol,2004,25(5):1495-1500.
[12]Li Y,Zhang Y,Yao Z,et al.Forkhead box Q1:A key player in the pathogenesis of tumors(review)[J].Int J Oncol,2016,49(1):51-58.
[13]Hong HK,Noveroske JK,Headon DJ,et al.The winged helix/forkhead transcription factor Foxq1 regulates differentiation of hair in satin mice[J].Genesis,2001,29(4):163-171.
[14]Hoggatt AM,Kriegel AM,Smith AF,et al.Hepatocyte nuclear factor-3 homologue 1(HFH-1)represses transcription of smooth muscle-specific genes[J].J Biol Chem,2000,275(40):31162-31170.
[15]Jensen EH,Lewis JM,Mcloughlin JM,et al.Down-regulation of pro-apoptotic genes is an early event in the progression of malignant melanoma[J].Ann Surg Oncol,2007,14(4):1416-1423.
[16]Zhang H,Meng F,Liu G,et al.Forkhead transcription factor foxq1promotes epithelial-mesenchymal transition and breast cancer metastasis[J].Cancer Res,2011,71(4):1292-1301.
[17]HU D,JIANG Z.Research progress of the correlation between FOXQ1 and gastrointestinal tumors[J].Medical Recapitulate,2015,21(15):2732-2735.[胡丹,姜政.FOXQ1与消化道肿瘤相关性的研究进展[J].医学综述,2015,21(15):2732-2735.]
[18]ZHANG S,XING JM,QIAN C,et al.Expression of Foxq1 and NF-κB p65 in cervical cancer and its clinical pathological significance[J].Academic Journal of Second Military Medical University,2009,30(3):300-304.[张甦,邢建明,钱琤,等.宫颈癌中Foxq1与NF-κB p65的表达及临床病理意义[J].第二军医大学学报,2009,30(3):300-304.]
[19]Zhang M,Xu Q,Yan S,et al.Suppression of forkhead box Q1 by microRNA-506 represses the proliferation and epithelial-mesenchymal transition of cervical cancer cells[J].Oncol Rep,2016,35(5):3106-3114.
[20]Qureshi R,Arora H,Rizvi MA.EMT in cervical cancer:Its role in tumour progression and response to therapy[J].Cancer Lett,2015,356(2 Pt B):321-331.
[21]LIU Huifang,CAO Mengting,XU Wei,et al.The transcription factors and their related signaling pathways in the regulation of tumor EMT[J].Modern Oncology,2017,25(13):2155-2160.[刘卉芳,曹梦婷,徐薇,等.调控肿瘤EMT的转录因子及其相关信号通路[J].现代肿瘤医学,2017,25(13):2155-2160.]
[22]Feng J,Xu L,Ni S,et al.Involvement of Fox Q1 in NSCLC through regulating EMT and increasing chemosensitivity[J].Oncotarget,2014,5(20):9689-9702.