G-蛋白偶联受体124与舌鳞癌的相关性研究
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摘要
目的:研究G-蛋白偶联受体124(GPCR124)在人舌鳞状细胞癌(TSCC)中的表达及其与患者临床病理指标及预后的关系。方法:收集南通大学附属医院及南通市肿瘤医院手术切除的TSCC组织标本,行第2代高通量测序鉴定、生物信息学分析,并筛选出TSCC相关基因GPCR124。蛋白质印迹法检测8对新鲜冰冻TSCC组织与邻近癌旁组织中GPCR124蛋白的表达;免疫组化SP法检测73例TSCC石蜡标本中GPCR124蛋白的表达水平,结合随访资料,分析GPCR124表达与临床病理指标及患者预后的相关性。结果:高通量测序结果显示TSCC组织较之配对癌旁组织中circ_0000231表达明显上调。蛋白质印迹法显示GPCR124蛋白在TSCC组织中明显高表达,而在配对癌旁组织中表达较低,其表达水平与肿瘤的分化程度(P=0.019)、临床分期(P=0.011)密切相关。Log-rank单因素分析结果显示肿瘤分化程度(P=0.000)、临床分期(P=0.000)与TSCC患者的生存预后相关,GPCR124表达水平低的患者生存率高于GPCR124表达水平高的患者。Cox风险回归模型的多因素分析显示,肿瘤的分化程度(P=0.038)、GPCR124表达水平(P=0.034)及临床分期(P=0.041)等均是TSCC预后不良的独立影响因素。结论:高通量测序及生物信息学分析表明GPCR124可能成为circ_0000231下游的靶向分子;GPCR124可能成为TSCC预后的一个独立影响因素,其高表达与TSCC的发生发展密切相关。
引文
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[3] 张春霞.miR_138_5p靶向调控DEK抑制舌癌迁移[D].合肥:安徽医科大学,2017.
[4] VALLON M,ROHDE F,JANSSEN K,et al.Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPaseRac and mediates contact inhibition of cell proliferation[J].Exp Cell Res,2010,316(3):412- 421.
[5] 卢先州,刘龙飞,周贤.肝细胞癌中GPR124的表达及与预后的关系[J].肿瘤防治研究,2014,41(10):1082- 1086.
[6] 郑建锋.GPR124在胃癌组织中的表达及意义[D].衡阳:南华大学,2015.
[7] 周贤.GPR124在结直肠癌组织中表达意义及与VEGF的相关性[D].衡阳:南华大学,2015.
[8] CARSON E B,WATKINS D N,NANDA A,et al.Cell surface tumor endothelial markers are conserved in mice and humans[J].Cancer Res,2001,61(18):6649- 6655.
[9] MATOS L L,DEDIVITIS R A,KULCSAR M A V,et al.External validation of the AJCC Cancer Staging Manual,8th edition,in an independent cohort of oral cancer patients[J].Oral Oncology,2017,71:47- 53.
[10]LYDIATT W M,PATEL S G,O'SUllIVAN B,et al.Head and neck cancers- major changes in the American Joint Committee on cancer eighth edition cancer staging manual[J].CA Cancer J Clin,2017,67(2):122- 137.
[11]LIU W,CHUN E,THOMPSON A A,et al.Structural basis for allosteric regulation of GPCRs by sodium ions[J].Science,2012,337(6091):232- 236.
[12]CULLEN M,ELZARRAD M K,SEAMAN S,et al.GPR124,an orphan G protein- coupled receptor,is required for CNS- specific vascularization and establishment of the blood- brain barrier[J].Proc Natl Acad Sci U S A,2011,108(14):5759- 5764.
[13]KUHNERT F,MANCUSO M R,SHAMLOO A,et al.Essential regulationof CNSangiogenesis by the orphan G protein- coupled receptor GPR124[J].Science,2010,330(6006):985- 989.
[14]VALLON M,ROHDE F,JANSSEN K P,et al.Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPaseRac and mediates contact inhibition of cell proliferation[J].Exp Cell Res,2010,316(3):412- 421.
[15]VALLON M,AUBELE P,JANSSEN K P,et al.Thrombin- induced shedding of tumour endothelial marker 5 and exposure of its RGD motif are regulated by cell- surface proteindisulfide- isomerase[J].Biochem J,2012,441(3):937- 944.
[16]VALLON M.Proteolytically processed soluble tumor endothelial marker(TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans[J].J Biol Chem,2006,281(45):34179- 34188.
[17]WANG Y,CHO S G,WU X,et al.G- protein coupled receptor 124 (GPR124) in endothelial cells regulates vascular endothelial growth factor(VEGF)- induced tumor angiogenesis[J].Curr Mol Med,2014,14(4):543- 554.
[18]COCQUERELLE C,MASCREZ B,HETUIN D,et al.Mis- splicing yields circular RNA molecules[J].FASEB J,1993,7(1):155- 160.
[19]SANGER H L,KLOTZ G,RIESNER D,et al.Viroids are single- stranded covalently closed circular RNA molecules existing as highly base- paired rod- like structures[J].Proc Natl Acad Sci U S A,1976,73(11):3852- 3856.
[20]QU S,YANG X,LI X,et al.Circular RNA:a new star of noncoding RNAs[J].Cancer Lett,2015,365(2):141- 148.