基于iTRAQ蛋白组学技术筛选的关键差异蛋白PCNA和MCM2在食管鳞癌中的表达及意义  

Expression and significance of PCNA and MCM2 in esophageal squamous cell carcinoma based on iTRAQ proteomics

作　　者：李超[1,2] 刘文颖 马遇庆[2] LI Chao;LIU Wenying;MA Yuqing(Department of RICU,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Pathology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院呼吸与呼吸危重症医学科,乌鲁木齐830054 [2]新疆医科大学第一附属医院病理科,乌鲁木齐830054

出　　处：《新疆医科大学学报》2021年第4期441-447,共7页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2020D01C246);新疆医科大学临床医学院高峰学科校内配套经费资助项目(33-0104006020801)。

摘　　要：目的探讨增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和微型染色体维持蛋白2(minichromosome maintenance proteins 2,MCM2)在食管鳞癌组织中的表达及临床意义。方法采用同位素标记的相对与绝对定量技术(isobaric tags for relative and absolute quantification,iTRAQ)检测6例新鲜食管鳞癌癌组织及癌旁正常组织,结合生物信息学分析获得关键差异表达基因。采用免疫组化EnVision两步法检测关键差异基因在118例食管鳞癌癌组织及癌旁正常组织中的表达,分析其表达与食管鳞癌临床病理特征的关系,通过基因表达谱交互分析(gene expression profiling interactive analysis, GEPIA)数据库比对分析预后。结果 (1)通过iTRAQ方法并结合生物信息学分析筛选出PCNA、MCM2作为关键基因;(2)PCNA在118例食管鳞癌中高表达率为56.8%(67/118),癌旁正常组织中为6.8%(8/118),二者差异有统计学意义(P<0.001);(3)MCM2在食管鳞癌的高表达率为80.5%(95/118),癌旁正常组织为15.3%(18/118),二者差异有统计学意义(P<0.001);(4)PCNA、MCM2在低分化组的表达率高于中分化和高分化组(P=0.011,P=0.009);(5)PCNA、MCM2在有淋巴结转移患者中的表达率均高于无淋巴结转移患者(P=0.002,P=0.035);(6)PCNA在IV期的表达率高于Ⅰ、Ⅱ、Ⅲ期(P=0.006),远处转移组中的表达高于无远处转移组(P=0.048),全层浸润的表达高于肌层浸润及黏膜层浸润组(P=0.006)。结论 PCNA及MCM2为促癌蛋白,可能参与了食管鳞癌的增殖、侵袭及转移,检测二者的表达对判断食管鳞癌的预后具有一定价值。Objective To investigate the expression and clinical significance of proliferating cell nuclear antigen(PCNA)and minichromosome maintenance proteins 2(MCM2)protein in esophageal squamous cell carcinoma(ESCC).Methods A total of 6 cases of fresh esophageal squamous cell carcinoma tissues and adjacent normal tissues were tested through isobaric tags for relative and absolute quantification(iTRAQ)method.The hub-genes were screened out by integrated bioinformatics analysis.The expressions of hub-genes in 118 cases of ESCC and adjacent normal tissues were evaluated by envision immunohistochemical method.The relationship between the expression of hub-genes and clinicopathological characteristics of ESCC was further analyzed.Finally,the prognosis was analyzed by comparing GEPIA(http://gepia.cancer-pku.cn/index.html)database.Results(1)PCNA and MCM2 were selected as hub-genes through iTRAQ method and bioinformatics analysis.(2)The high expression rate of PCNA was 56.8%(67/118)and6.8%(8/118)in esophageal squamous cell carcinoma and adjacent normal tissues,and the difference between the two groups was statistically significant(P<0.001);(3)The high expression rate of MCM2 in esophageal squamous cell carcinoma and adjacent normal tissues was 80.5%(95/118)and 15.3%(18/118),the difference was statistically significant(P<0.001);(4)The high expression rate of PCNA and MCM2 in poor differentiation group was higher than that in moderate differentiation and high differentiation group(P=0.011,P=0.009);(5)The high expression rate of PCNA and MCM2 in lymph node metastasis group was higher than that in non-lymph node metastasis group(P=0.002,P=0.035);(6)The expression of PCNA in stageⅣwas higher than that in stageⅠ,ⅡandⅢ(P=0.006),and the expression in distant metastasis group was higher than that in non-distant metastasis group(P=0.048),and the expression of esophageal invasion in whole layer was higher than that in muscle and mucous layer(P=0.006).Conclusion PCNA and MCM2 are oncogenic proteins,which may be involved in the proli

关 键 词：食管鳞癌 同位素标记的相对与绝对定量技术 增殖细胞核抗原 微小染色体维持蛋白2 

分 类 号：R714.21[医药卫生—妇产科学]