应用iTRAQ技术筛选预测食管鳞癌放化疗疗效优势蛋白的研究

目的:利用同位素标记相对和绝对定量（iTRAQ）技术筛选预测食管鳞癌放化疗疗效的血清差异蛋白，以指导临床个体化治疗。方法:纳入52例诊断明确的局部晚期和晚期食管鳞癌患者，行规范放化疗，判断疗效及长期随访，同时收集患者治疗前、后血清。应用iTRAQ技术筛选放化疗疗效相关的血清差异蛋白。应用Uniprot、KEGG等数据库对差异蛋白进行生物学分析，筛选出与肿瘤相关、具有核心作用且介导肿瘤相关通路的优势蛋白。结果:疗效评价结果:放化疗敏感组（CR+PR）食管癌患者占59.62%（31/52例）；放化疗抗拒组（SD+PD）占40.38%（21/52例）。放化疗敏感组对比放化疗抗拒组:共筛选出17个有显著差异的差异蛋白，其中上调蛋白为脂联素（ADIPOQ）、IgL C7、血清转铁蛋白（TF）、中性粒细胞防御素（DEFA1）共4个，下调蛋白为聚合物免疫球蛋白受体（PIGR）、单核细胞分化抗原14（CD14）等13个。KEGG通路分析显示，TF、CD14可能分别参与HIF-1、MAPK信号通路的调节。结论:食管鳞癌患者外周血中能够筛选出预测放化疗疗效的潜在优势蛋白，并参与一些关键通路；TF、ADIPOQ、PIGR、CD14对于食管鳞癌放化疗疗效具有潜在的预测价值。

Screening of the dominant protein of predicting efficacy of chemoradiotherapy in esophageal squamous cancinoma by iTRAQ technology

Objective:Using isotope labeled relative and absolute quantification(iTRAQ) technology screening of esophageal squamous cancer radiotherapy and chemotherapy efficacy and survival of serum differential proteins，and guiding the individualized treatment.Methods:All 52 patients with definite diagnosis of local and advanced esophageal squamous cell carcinoma were treated with standardized radiotherapy，and with long-term follow-up.Using iTRAQ technology to screen and radiate the therapeutic effect of relevant differential proteins.Using Uniprot，KEGG and other databases to conduct biological analysis of the differential protein，and then screened the dominant protein with relevant pathway mediated by tumor related，core protein.Results:Follow-up results of short-term follow-up:59.62%(31/52) patients with esophageal cancer(CR+PR) and 40.38%(21/52) patients with resistance to radiochemotherapy（SD+PD).Radiochemotherapy-sensitive group vs radiochemotherapy-resistant group:A total of 17 significantly differentially expressed proteins were screened out，among which there were up-regulated proteins ADIPOQ（adiponectin)，IgL C7，TF(serum transferrin)，DEFA1(neutrophil defense A） total of four factors，13 down-regulated protein PIGR(polymer immunoglobulin receptor)，CD14（monocyte differentiation antigen 14）.By KEGG pathway analysis，TF，CD14 may be involved in the regulation of HIF-1 signaling pathway，MAPK signaling pathway，respectively.Conclusion:The potential predominant proteins predicting the efficacy of esophageal squamous cell carcinoma can be screened from the peripheral blood and involved in some key pathways.TF，ADIPOQ，PIGR，CD14 for esophageal squamous cell carcinoma chemotherapy may have potential predicting value.