端粒重复序列结合因子1和2在口腔黏膜癌组织中的表达及临床意义
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摘要
目的研究端粒重复序列结合因子(telomere repeat binding factor,TRF) 1、TRF2在口腔黏膜癌组织中的表达情况及临床意义。方法收集2012年7月—2016年7月武汉大学人民医院收治的48例口腔黏膜癌患者癌组织和癌旁组织标本以及32例正常人口腔软组织表本,采用免疫组化方法来检测癌组织、癌旁组织和正常人口腔软组织标本中TRF1与TRF2蛋白的表达情况。结果口腔黏膜癌组织中TRF1的阳性率明显低于癌旁组织和正常组织(P<0. 01),并且高分化与中分化癌组织中TRF1的阳性率显著高于低分化癌组织(P<0. 05)。癌组织中TRF2阳性率显著高于癌旁组织与正常组织(P<0. 01),在高分化与中分化癌组织中TRF2阳性率明显低于低分化癌组织(P<0. 05)。结论 TRF1的阳性率在癌组织中明显降低,而TRF2的阳性率在癌组织中显著升高,表明TRF1与TRF2蛋白表达水平的变化可能与口腔黏膜癌的发生发展密切相关。
Objective To elucidate the expression and clinical significance of telomere repeat binding factor( TRF) 1,TRF2 in oral squamous cell carcinoma. Methods Immunohistochemistry staining was used to detect the expression of TRF1 and TRF2 in 48 cases of oral mucosa carcinoma and adjacent tissues,and 32 cases of normal oral soft tissues collected in Renmin Hospital of Wuhan University from July 2012 to July 2016. Results The positive rate of TRF1 in oral mucosal cancer tissues was significantly lower than that in adjacent tissues and normal tissues( P < 0. 01),and the positive rate of TRF1 in highly differentiated and moderately differentiated oral mucosal cancer tissues was significantly higher than that in poorly differentiated oral mucosal cancer tissues( P<0. 05). The positive rate of TRF2 in oral mucosal cancer tissues was significantly higher than that in paracancerous and normal tissues( P<0. 01),and its positive rate was significantly lower in highly differentiated and moderately differentiated oral mucosal cancer tissues than that in poorly differentiated oral mucosal cancer tissues( P<0. 05). Conclusion The positive rate of TRF1 was significantly decreased in oral mucosal cancer tissues,while the positive rate of TRF2 was significantly increased. These results suggest that the levels of TRF1 and TRF2 expression may be closely related to the development of oral carcinoma.
Objective To elucidate the expression and clinical significance of telomere repeat binding factor( TRF) 1,TRF2 in oral squamous cell carcinoma. Methods Immunohistochemistry staining was used to detect the expression of TRF1 and TRF2 in 48 cases of oral mucosa carcinoma and adjacent tissues,and 32 cases of normal oral soft tissues collected in Renmin Hospital of Wuhan University from July 2012 to July 2016. Results The positive rate of TRF1 in oral mucosal cancer tissues was significantly lower than that in adjacent tissues and normal tissues( P < 0. 01),and the positive rate of TRF1 in highly differentiated and moderately differentiated oral mucosal cancer tissues was significantly higher than that in poorly differentiated oral mucosal cancer tissues( P<0. 05). The positive rate of TRF2 in oral mucosal cancer tissues was significantly higher than that in paracancerous and normal tissues( P<0. 01),and its positive rate was significantly lower in highly differentiated and moderately differentiated oral mucosal cancer tissues than that in poorly differentiated oral mucosal cancer tissues( P<0. 05). Conclusion The positive rate of TRF1 was significantly decreased in oral mucosal cancer tissues,while the positive rate of TRF2 was significantly increased. These results suggest that the levels of TRF1 and TRF2 expression may be closely related to the development of oral carcinoma.
引文
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[11] Tan R,Nakajima S,Wang Q,et al.Nek7 protects telomeres from oxidative DNA damage by phosphorylation and stabilization of TRF1[J].Mol Cell,2017,65(5):818-831.
[12] Lan J,Zhu Y,Xu L,et al. The 68-k Da telomeric repeat binding factor 1(TRF1)-associated protein(TAP68)interacts with and recruits TRF1 to the spindle pole during mitosis[J].J Biol Chem,2014,289(20):14145-14156.
[13] Walker JR,Zhu XD. Post-translational modifications of TRF1 and TRF2 and their roles in telomere maintenance[J].Mech Ageing Dev,2012,133(6):421-434.
[14] Lin J,Countryman P,Buncher N,et al. TRF1 and TRF2use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres[J].Nucleic Acids Res,2014,42(4):2493-2504.
[15] Kim H,Lee OH,Xin H,et al.TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs[J]. Nat Struct Mol Biol,2009,16(4):372-379.
[16] Galati A,Micheli E,Alicata C,et al. TRF1 and TRF2binding to telomeres is modulated by nucleosomal organization[J].Nucleic Acids Res,2015,43(12):5824-5837.
[17] Boskovic J,Martinez-Gago J,Mendez-Pertuz M,et al.Molecular architecture of full-length TRF1 favors its interaction with DNA[J]. J Biol Chem,2016,291(41):21829-21835.
[2] Arora A,Husain N,Bansal A,et al.Development of a new outcome prediction model in early-stage squamous cell carcinoma of the oral cavity based on histopathologic parameters with multivariate analysis:the aditi-nuzhat lymph-node prediction score(ANLPS)system[J]. Am J Surg Pathol,2017,41(7):950-960.
[3] Benhamou Y,Picco V,Pagès G.The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma[J].Oral Oncol,2016,57:46-53.
[4] Carkic J,Nikolic N,Radojevic-Skodric S,et al.The role of TERT-CLPTM1L SNPs,h TERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma[J].J Oral Sci,2016,58(4):449-458.
[5] Bejarano L,Schuhmacher AJ,Méndez M,et al.Inhibition of TRF1 telomere protein impairs tumor initiation and progression in glioblastoma mouse models and patient-derived xenografts[J].Cancer Cell,2017,32(5):590-607.
[6] Wieczór M,Czub J.How proteins bind to DNA:target discrimination and dynamic sequence search by the telomeric protein TRF1[J]. Nucleic Acids Res,2017,45(13):7643-7654.
[7] Frescas D,de Lange T.TRF2-tethered TIN2 can mediate telomere protection by TPP1/POT1[J]. Mol Cell Biol,2014,34(7):1349-1362.
[8]陈炜,何丽娜,王勇,等.端粒重复序列结合蛋白TRF1及TRF2在前列腺癌中的表达及临床意义[J].临床泌尿外科杂志,2016,31(9):841-845.
[9]栗晓玲,马金辉,萧福元,等.嚼槟榔与口腔癌关系的病例对照研究[J].实用预防医学,2016,23(9):1059-1062.
[10] Niranjan KC,Sarathy NA.Prognostic impact of tumor-stroma ratio in oral squamous cell carcinoma-a pilot study[J].Ann Diagn Pathol,2018,35:56-61.
[11] Tan R,Nakajima S,Wang Q,et al.Nek7 protects telomeres from oxidative DNA damage by phosphorylation and stabilization of TRF1[J].Mol Cell,2017,65(5):818-831.
[12] Lan J,Zhu Y,Xu L,et al. The 68-k Da telomeric repeat binding factor 1(TRF1)-associated protein(TAP68)interacts with and recruits TRF1 to the spindle pole during mitosis[J].J Biol Chem,2014,289(20):14145-14156.
[13] Walker JR,Zhu XD. Post-translational modifications of TRF1 and TRF2 and their roles in telomere maintenance[J].Mech Ageing Dev,2012,133(6):421-434.
[14] Lin J,Countryman P,Buncher N,et al. TRF1 and TRF2use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres[J].Nucleic Acids Res,2014,42(4):2493-2504.
[15] Kim H,Lee OH,Xin H,et al.TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs[J]. Nat Struct Mol Biol,2009,16(4):372-379.
[16] Galati A,Micheli E,Alicata C,et al. TRF1 and TRF2binding to telomeres is modulated by nucleosomal organization[J].Nucleic Acids Res,2015,43(12):5824-5837.
[17] Boskovic J,Martinez-Gago J,Mendez-Pertuz M,et al.Molecular architecture of full-length TRF1 favors its interaction with DNA[J]. J Biol Chem,2016,291(41):21829-21835.