CAJ | 학술논문

目的：分析c-Jun在鼻咽癌组织中的表达以及对鼻咽癌复发的影响。方法选择2003年1月~2005年9月在温州医学院附属第一医院耳鼻喉科行放疗的4例复发鼻咽癌(复发鼻咽癌组)和4例初发鼻咽癌患者(初发鼻咽癌组)的组织标本，应用磷酸化抗体蛋白质芯片筛选初发鼻咽癌组与复发鼻咽癌组患者鼻咽癌组织中的差异磷酸化蛋白，并进行聚类。并选取其中的差异磷酸化蛋白进行免疫组化试验验证，用于免疫组化验证的初发及复发鼻咽癌组织40例取自2003年8月~2010年5月温州医学院附属第一医院病理科，将其分为初发鼻咽癌组(n=20)和复发鼻咽癌组(n=20)。结果在复发鼻咽癌组和初发鼻咽癌组中筛选出包括c-Jun(P=0.030)、Histone H2A(P=0.044)、SEK1(P=0.048)、KIT(P=0.042)、ATP1A1(P=0.007)和Synapsin(P=0.023)共6个差异蛋白，复发鼻咽癌组中Histone H2A(上调比率为1.08)、SEK1(上调比率为1.14)、KIT(上调比率为1.22)、ATP1A1(上调比率为1.22)和Synapsin(上调比率为1.22)磷酸化水平较初发鼻咽癌组患者上调，复发鼻咽癌组中c-Jun磷酸化水平较初发鼻咽癌组患者下调(下调比率为0.87)。其中c-Jun、Histone H2AX、SEK1及KIT蛋白质的磷酸化水平改变可能与鼻咽癌复发机制有关。通过免疫组化验证了c-Jun在复发鼻咽癌组低于初发鼻咽癌组，差异有统计学意义(P=0.048)。结论磷酸化c-Jun在复发鼻咽癌组织中低表达，c-Jun磷酸化涉及调控基因、抑制细胞凋亡、促细胞增殖等信号转导通路，可能与肿瘤复发有关，还可提示预后及提供治疗靶点。
목적：분석c-Jun재비인암조직중적표체이급대비인암복발적영향。방법선택2003년1월~2005년9월재온주의학원부속제일의원이비후과행방료적4례복발비인암(복발비인암조)화4례초발비인암환자(초발비인암조)적조직표본，응용린산화항체단백질심편사선초발비인암조여복발비인암조환자비인암조직중적차이린산화단백，병진행취류。병선취기중적차이린산화단백진행면역조화시험험증，용우면역조화험증적초발급복발비인암조직40례취자2003년8월~2010년5월온주의학원부속제일의원병이과，장기분위초발비인암조(n=20)화복발비인암조(n=20)。결과재복발비인암조화초발비인암조중사선출포괄c-Jun(P=0.030)、Histone H2A(P=0.044)、SEK1(P=0.048)、KIT(P=0.042)、ATP1A1(P=0.007)화Synapsin(P=0.023)공6개차이단백，복발비인암조중Histone H2A(상조비솔위1.08)、SEK1(상조비솔위1.14)、KIT(상조비솔위1.22)、ATP1A1(상조비솔위1.22)화Synapsin(상조비솔위1.22)린산화수평교초발비인암조환자상조，복발비인암조중c-Jun린산화수평교초발비인암조환자하조(하조비솔위0.87)。기중c-Jun、Histone H2AX、SEK1급KIT단백질적린산화수평개변가능여비인암복발궤제유관。통과면역조화험증료c-Jun재복발비인암조저우초발비인암조，차이유통계학의의(P=0.048)。결론린산화c-Jun재복발비인암조직중저표체，c-Jun린산화섭급조공기인、억제세포조망、촉세포증식등신호전도통로，가능여종류복발유관，환가제시예후급제공치료파점。
Objective To analyze expression of c-jun in nasopharyngeal carcinoma and the effects on the recurrent na-sopharyngeal carcinoma. Methods Four primary nasopharyngeal carcinoma tissues (pNPC group) and four relapsed na-sopharyngeal carcinoma tissues (rNPC group) were obtained from the Department of Otolaryngology, the First Affiliated Hospital of Wenzhou Medical College. The differentially phosphorylation level of proteins in rNPC group and pNPC group were identified by Full Moon BioSystems' Phospho Explorer antibody array and this was followed by cluster anal-ysis. Immunohistochemistry was performed on some of differentially phosphorylated protein 40 cases of primary and re-lapsed nasopharyngeal carcinoma tissues were selected for immunohistochemical validation, from August 2003 to May 2010 in Pathology Department of the First Affiliated Hospital of Wenzhou Medical College, and they were divided into primary nasopharyngeal carcinoma group (n=20) and relapsed nasopharyngeal carcinoma group (n=20). Results The phosphorylation levels of proteins in two groups were different and six significantly differentially phosphorylated pro-teins were identified including c-Jun (P=0.030), Histone H2A (P=0.044), SEK1 (P=0.048), KIT (P=0.042), ATP1A1 (P=0.007), and Synapsin (P=0.023). Among them, compared to pNPC group the phosphorylation levels of five proteins (ATP1A1, Histone H2A, KIT, SEK1 and Synapsin) in tissues of the rNPC group were increased, the up-regulated ratio was 1.08, 1.14, 1.22, 1.22, 1.22 respectively, and one protein was decreased (c-Jun), the down-regulated ratio of c-Jun was 0.87. Some of the diferentially phosphorylated proteins including c-Jun, Histone H2AX, SEK1 and KIT maybe play crucial roles in the recurrence of NPC. The phosphorylation levels of c-Jun was also decreased in rNPC group(P=0.048) by immunohistochemistry. Conclusion The phosphorylation levels of c-Jun is decrease in tissues of rNPC, which maybe play crucial roles in the recurrence of NPC. The phosphorylated c-Jun participates in the processes of DNA damage re-pair, apoptosis, cell migration, invasion, signal transduction and so on, and may indicates prognosis and provides thera-putic targets.