整合素连接激酶和Toll样受体-2在眼附属器黏膜相关淋巴组织淋巴瘤中的表达及其对预后的影响
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摘要
目的研究整合素连接激酶(integrin linked kinase,ILK)与Toll样受体-2(Toll like receptors-2,TLR-2)在眼附属器黏膜相关淋巴组织(mucosa-associated lymphatic tissue,MALT)淋巴瘤中的表达及其对患者生存状况的影响。方法收集46例(46眼)符合眼附属器MALT淋巴瘤诊断标准的患者病灶组织标本,运用免疫组织化学染色法测定其ILK与TLR-2的蛋白表达情况,分析ILK与TLR-2蛋白与患者临床病理特征的关系;同时探讨ILK与TLR-2蛋白表达情况与患者预后的关系。结果患者瘤组织中的ILK与TLR-2蛋白表达阳性率分别为67.4%(31/46)、71.7%(33/46)。患者瘤组织中ILK、TLR-2蛋白表达阳性率均与性别、年龄、病灶部位均无关(均为P>0.05),均与Ann Arbor临床分期相关(均为P<0.05)。ILK蛋白表达阳性患者的生存期(治疗结束至随访末期的时间)为(21.5±2.7)个月,低于ILK蛋白表达阴性患者的生存期(29.2±2.1)个月(P<0.05);TLR-2蛋白表达阳性患者的生存期为(20.4±1.7)个月,低于TLR-2蛋白表达阴性患者的生存期(27.6±2.3)个月(P<0.05)。结论 ILK、TLR-2与眼附属器MALT淋巴瘤的生物学行为密切相关;联合检测ILK、TLR-2对此类疾病诊断及患者预后具有一定的指导价值。
Objective To investigate the expression of integrin-linked kinase( ILK) and Toll-like receptor( TLR-2) in ocular adnexal mucosa-associated lymphoid tissue( MALT) lymphoma and the effects on patients' outcomes. Methods Tissue specimens from 46 patients with MALT lymphoma were collected in this study. The expression of ILK and TLR-2 protein was detected by immunohistochemical methods,and the correlation of ILK and TLR-2 protein expression with clinicopathological features and patients ' outcomes was analyzed. Results The positive rates of ILK and TLR-2 protein expression in tumor tissues were 67. 4%( 31/46) and 71. 7%( 33/46),respectively,which was related to the clinical stage of Ann Arbor( P < 0. 05),rather than to sex,age and lesion location( all P > 0. 05). The survival of patients with ILK positive expression was less than that of ones with ILK negative expression [( 21. 5 ± 2. 7) months vs.( 29.2 ± 2. 1) months]( P < 0. 05); meanwhile,the survival of patients with TLR-2 positive expression was less than that of ones with TLR-2 negative expression [( 20. 4 ± 1. 7) months v.( 27. 6 ± 2.3) months]( P < 0. 05). Conclusion ILK and TLR-2 are closely related to biological behavior of ocular adnexal MALT lymphoma,and combination detection of ILK and TLR-2 has a certain guiding value for diagnosis and prognosis.
Objective To investigate the expression of integrin-linked kinase( ILK) and Toll-like receptor( TLR-2) in ocular adnexal mucosa-associated lymphoid tissue( MALT) lymphoma and the effects on patients' outcomes. Methods Tissue specimens from 46 patients with MALT lymphoma were collected in this study. The expression of ILK and TLR-2 protein was detected by immunohistochemical methods,and the correlation of ILK and TLR-2 protein expression with clinicopathological features and patients ' outcomes was analyzed. Results The positive rates of ILK and TLR-2 protein expression in tumor tissues were 67. 4%( 31/46) and 71. 7%( 33/46),respectively,which was related to the clinical stage of Ann Arbor( P < 0. 05),rather than to sex,age and lesion location( all P > 0. 05). The survival of patients with ILK positive expression was less than that of ones with ILK negative expression [( 21. 5 ± 2. 7) months vs.( 29.2 ± 2. 1) months]( P < 0. 05); meanwhile,the survival of patients with TLR-2 positive expression was less than that of ones with TLR-2 negative expression [( 20. 4 ± 1. 7) months v.( 27. 6 ± 2.3) months]( P < 0. 05). Conclusion ILK and TLR-2 are closely related to biological behavior of ocular adnexal MALT lymphoma,and combination detection of ILK and TLR-2 has a certain guiding value for diagnosis and prognosis.
引文
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[6]DE SOUZA DR,SANABANI SS,DE SOUZA AC.Prognostic impact of MYCN,DDX1,Trk A,and Trk C gene transcripts expression in neuroblastoma[J].Pediatr Blood Cancer,2011,56(5):749-756.
[7]GULATI S,CORRA ZM,KARIM N,MEDLIN S.Ocular adnexal lymphoma presenting with visual loss[J].Am J Med Sci,2016,8(1):56-60.
[8]BHARDWAJ M,SHARMA A,SEN S,KUMAR L,SATPATHY G,KASHYAP S,et al.Chlamydia,and ocular adnexal lymphomas:An Indian experience[J].Exp Mol Pathol,2016,101(1):74-80.
[9]JUNG SK,PAIK JS,JUNG SE,PARK G,CHOI BO,OH JK,et al.Suggestion of response evaluation criteria in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma(OAML)[J].Ann Hematol,2015,94(7):1185-1193.
[10]STAGNER AM,JAKOBIEC FA,FREITAG SK.Primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin:Diagnostic clues and distinction from other ocular adnexal diseases[J].Sur Ophthalmol,2015,61(3):333-338.
[11]DONG L.Expression and significance of Hsp90 and its client protein ILK in gastric cancer and precancerous lesion[J].Chin J Int Trad West Med Digest,2016,24(4):271-274.董梁.Hsp90及其受体蛋白ILK在胃癌及癌前病变中的表达及意义[J].中国中西医结合消化杂志,2016,24(4):271-274.
[12]DAI J,MATSUI T,ABEL ED,DEDHAR S,GERSZTEN RE,SEIDMAN CE,et al.Deep sequence analysis of gene expression identifies osteopontin as a downstream effector of integrin-linked kinase(ILK)in cardiac-specific ILK knockout mice[J].Circ Heart Fail,2014,7(1):184-193.
[13]LEGATE KR,MONTAEZ E,KUDLACEK O,FSLER R.ILK,PINCH and parvin:the t IPP of integrin signalling[J].Nat Rev Mol Cell Biol,2006,7(1):20-31.
[14]JIN M,CUI JW,LIU XL,SU JJ,WANG WS.Study on antidepressant effect of toll-like receptor 2 inhibitor C29 and its mechanism[J].J Xinxiang Med Univ,2017,34(6):460-464.靳玫,崔俊伟,刘晓利,宿俊杰,王文晟.TOLL样受体2抑制剂C29的抗抑郁效应及其机制[J].新乡医学院学报,2017,34(6):460-464.
[15]XIONG Y,SUN W,WANG Z,TU Y,LIU XF,LIANG H.TLR2signaling pathways promote secretion of Foxp3 and VEGF in lung cancer cells[J].Chin J Immunol,2014,30(9):1174-1177.熊莺,孙午,王志,涂艳,刘晓峰,梁皓.肺癌细胞中TLR2信号通路促进Foxp3和VEGF分泌的研究[J].中国免疫学杂志,2014,30(9):1174-1177.
[16]ZHANG C,ZHANG QY,ZHANG MH,LU KP,WANG Y,ZHAO S.Expression and clinical significance of TLR-2 and TLR-5 in diffuse large B-cell lymphoma[J].Clin Oncol,2013,18(5):412-415.张翠,张清媛,张明辉,卢康平,王燕,赵曙.TLR-2和TLR-5在弥漫大B细胞淋巴瘤组织中的表达及临床意义[J].临床肿瘤学杂志,2013,18(5):412-415.
[17]CHANG LH,PAN SL,LAI CY,TSAI AC,TENG CM.Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-αexpression and MEK/VEGF-A-mediated angiogenesis[J].Am J Pathol,2013,183(2):566-575.
[18]ZELJIC K,SUPIC G,JOVIC N,KOZOMARA R,BRANKOVICMAGIC M,OBRENOVIC M,et al.Association of TLR2,TLR3,TLR4 and CD14 genes polymorphisms with oral cancer risk and survival[J].Oral Diseases,2014,20(4):416-424.
[2]DESAI A,JOAG MG,LEKAKIS L,CHAPMAN JR,VEGA F,TIBSHIRANI R,et al.Long-term course of patients with primary ocular adnexal MALT lymphoma:a large single-institution cohort study[J].Blood,2017,129(3):324-332.
[3]OHGA S,NAKAMURA K,SHIOYAMA Y,SASAKI T,YAMAGUCHI T,YOSHITAKE T,et al.Treatment outcome of radiotherapy for localized primary ocular adnexal MALT lymphoma-prognostic effect of the ajcc tumor-node-metastasis clinical staging system[J].Anticancer Res,2015,35(6):3591-3597.
[4]GUAN YY.Expression and Significances of integrin-linked kinase and nitric oxide synthase in oral squamous cell carcinoma[J].J Oral Sci Res,2016,32(5):527-530.管永昱.整合素连接激酶和一氧化氮合酶在口腔鳞状细胞癌中的表达及意义[J].口腔医学研究,2016,32(5):527-530.
[5]LI KY,XIONG SD,XIONG WN.Effects of Toll-like receptor 2 signaling on expression of interleukin-17 in EL4 T cells[J].Acta Medi Univ Sci Technol Huazhong,2011,40(5):517-520.李开艳,熊盛道,熊维宁.Toll样受体2信号对小鼠淋巴瘤EL4细胞系表达IL-17的影响[J].华中科技大学学报医学版,2011,40(5):517-520.
[6]DE SOUZA DR,SANABANI SS,DE SOUZA AC.Prognostic impact of MYCN,DDX1,Trk A,and Trk C gene transcripts expression in neuroblastoma[J].Pediatr Blood Cancer,2011,56(5):749-756.
[7]GULATI S,CORRA ZM,KARIM N,MEDLIN S.Ocular adnexal lymphoma presenting with visual loss[J].Am J Med Sci,2016,8(1):56-60.
[8]BHARDWAJ M,SHARMA A,SEN S,KUMAR L,SATPATHY G,KASHYAP S,et al.Chlamydia,and ocular adnexal lymphomas:An Indian experience[J].Exp Mol Pathol,2016,101(1):74-80.
[9]JUNG SK,PAIK JS,JUNG SE,PARK G,CHOI BO,OH JK,et al.Suggestion of response evaluation criteria in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma(OAML)[J].Ann Hematol,2015,94(7):1185-1193.
[10]STAGNER AM,JAKOBIEC FA,FREITAG SK.Primary cutaneous extranodal marginal zone B-cell lymphoma of the eyelid skin:Diagnostic clues and distinction from other ocular adnexal diseases[J].Sur Ophthalmol,2015,61(3):333-338.
[11]DONG L.Expression and significance of Hsp90 and its client protein ILK in gastric cancer and precancerous lesion[J].Chin J Int Trad West Med Digest,2016,24(4):271-274.董梁.Hsp90及其受体蛋白ILK在胃癌及癌前病变中的表达及意义[J].中国中西医结合消化杂志,2016,24(4):271-274.
[12]DAI J,MATSUI T,ABEL ED,DEDHAR S,GERSZTEN RE,SEIDMAN CE,et al.Deep sequence analysis of gene expression identifies osteopontin as a downstream effector of integrin-linked kinase(ILK)in cardiac-specific ILK knockout mice[J].Circ Heart Fail,2014,7(1):184-193.
[13]LEGATE KR,MONTAEZ E,KUDLACEK O,FSLER R.ILK,PINCH and parvin:the t IPP of integrin signalling[J].Nat Rev Mol Cell Biol,2006,7(1):20-31.
[14]JIN M,CUI JW,LIU XL,SU JJ,WANG WS.Study on antidepressant effect of toll-like receptor 2 inhibitor C29 and its mechanism[J].J Xinxiang Med Univ,2017,34(6):460-464.靳玫,崔俊伟,刘晓利,宿俊杰,王文晟.TOLL样受体2抑制剂C29的抗抑郁效应及其机制[J].新乡医学院学报,2017,34(6):460-464.
[15]XIONG Y,SUN W,WANG Z,TU Y,LIU XF,LIANG H.TLR2signaling pathways promote secretion of Foxp3 and VEGF in lung cancer cells[J].Chin J Immunol,2014,30(9):1174-1177.熊莺,孙午,王志,涂艳,刘晓峰,梁皓.肺癌细胞中TLR2信号通路促进Foxp3和VEGF分泌的研究[J].中国免疫学杂志,2014,30(9):1174-1177.
[16]ZHANG C,ZHANG QY,ZHANG MH,LU KP,WANG Y,ZHAO S.Expression and clinical significance of TLR-2 and TLR-5 in diffuse large B-cell lymphoma[J].Clin Oncol,2013,18(5):412-415.张翠,张清媛,张明辉,卢康平,王燕,赵曙.TLR-2和TLR-5在弥漫大B细胞淋巴瘤组织中的表达及临床意义[J].临床肿瘤学杂志,2013,18(5):412-415.
[17]CHANG LH,PAN SL,LAI CY,TSAI AC,TENG CM.Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-αexpression and MEK/VEGF-A-mediated angiogenesis[J].Am J Pathol,2013,183(2):566-575.
[18]ZELJIC K,SUPIC G,JOVIC N,KOZOMARA R,BRANKOVICMAGIC M,OBRENOVIC M,et al.Association of TLR2,TLR3,TLR4 and CD14 genes polymorphisms with oral cancer risk and survival[J].Oral Diseases,2014,20(4):416-424.