高细胞亚型甲状腺乳头状癌临床病理分析与蛋白质组学研究  

Clinicopathological analysis and proteomics study of tall cell subtype papillary thyroid carcinoma(TC-PTC)

作　　者：王维娜[1] 陈海霞[1] 张焕[1] 杨波[1] 蒲红伟[2] WANG Weina;CHEN Haixia;ZHANG Huan;YANG Bo;PU Hongwei(Department of Pathology,the Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi 830011,China;Subject Construction Department,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院病理科,乌鲁木齐830011 [2]新疆医科大学第一附属医院学科建设科,乌鲁木齐830011

出　　处：《新疆医科大学学报》2023年第11期1418-1423,1431,共7页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区卫生健康青年医学科技人才专项项目(WJWY-202152);新疆维吾尔自治区自然科学基金项目(2021D01C408)。

摘　　要：目的探讨高细胞亚型甲状腺乳头状癌(TC-PTC)临床病理学特征,并研究高细胞亚型PTC蛋白质谱,通过生物信息学分析,筛选与鉴定高细胞亚型甲状腺乳头状癌差异表达蛋白,寻找TC-PTC潜在生物标志物。方法收集2021年1月至2021年6月期间新疆医科大学附属肿瘤医院67例甲状腺乳头状癌患者术后标本,经病理诊断确诊,TC-PTC17例,经典型甲状腺乳头状癌(CPTC)50例,对比分析两组的临床病理学特征。同时收集其中17例TC-PTC,15例CPTC新鲜手术切除标本,另收集15例良性甲状腺结节(BTN)新鲜标本,应用蛋白质非标记定量技术(label-free)结合液相色谱与串联质谱技术(LC-MS/MS),鉴定和筛选高细胞亚型甲状腺乳头状癌差异表达蛋白,GO及KEGG分析差异蛋白的生物学功能及富集的信号通路。结果TC-PTC组更易出现多发病灶、侵犯甲状腺被膜及淋巴结转移,差异无统计学意义(P>0.05),TC-PTC组具有更大的肿瘤体积,差异有统计学意义(P<0.05)。3组共分离和鉴定肽段数34294个,蛋白质总数4739个。与CPTC组及BTN组相比,TC-PTC组显著高表达的蛋白14个(FC≥1.3,P<0.05),其中6个蛋白是TC-PTC特定表达蛋白,分别是:NRP1、MTM1、COG1、SRP19、PRR15、CDC2L5。利用GO及KEGG通路分析,发现差异蛋白主要参与代谢、基因表达及翻译、生物合成等生物学过程,发挥结合、酶调节活性、催化活性等分子功能;主要富集于核糖体生物合成、蛋白酶体系统、剪接体组成、磷酸戊糖途径等信号通路。进一步根据文献复习,我们筛选出4个可能与TC-PTC发生进展相关的蛋白,分别是:CD73、SNRPA1、NAPRT、NRP1。结论TC-PTC临床生物学行为更具有侵袭性和更高的临床T分期;TC-PTC与CPTC、BTN间存在高表达的差异蛋白,筛选的差异蛋白可能成为高细胞亚型甲状腺乳头状癌潜在分子标志物和治疗靶点。Objective To investigate the clinicopathological features and protein profiles of tall cell subtype papillary thyroid carcinoma(TC-PTC),the differentially expressed proteins of TC-PTC were screened and identified,and the potential biomarkers of TC-PTC were found by bioinformatics.Methods A total of 67 cases of PTC samples were obtained from the patients who underwent surgery at the hospital from January 2021 to June 2021,and confirmed by pathological diagnosis,including 17 TC-PTC and 50 cases of classic papillary thyroid carcinoma(CPTC),the clinicopathological features of the 2 groups were compared and analyzed.At the same time,17 TC-PTC,15 CPTC and 15 cases of benign thyroid nodules(BTN)fresh surgical resection specimens were collected with using label-free quantification combined with liquid chromatography and tandem mass spectrometry(LC-MS/MS)quantitative proteomics technology.Identifying and screening the differentially expressed proteins in TC-PTC and the biological functions and enriched signaling pathways of differential proteins were analyzed by GO and KEGG.Results TC-PTC group was more likely to have multiple lesions,invasion of thyroid capsule and lymph node metastasis,with no statistical significance(P>0.05),while TC-PTC group had larger tumor volume,with statistical significance(P<0.05).A total of 34294 peptides and 4739 proteins were isolated and identified in the 3 groups.Compared with CPTC group and BTN group,14 proteins were significantly overexpressed in TC-PTC group(FC≥1.3,P<0.05),among which 6 proteins were specific expression proteins of TC-PTC,namely NRP1,MTM1.COG1,SRP19,PRR15 and CDC2L5.By using GO and KEGG pathway analysis,it was found that differential proteins were mainly involved in biological processes such as metabolism,gene expression,translation and biosynthesis,and played molecular functions such as binding,enzyme regulation activity,and catalytic activity.It is mainly concentrated in signaling pathways such as ribosome biosynthesis,proteasome pathway,spliceosome composition and p

关 键 词：高细胞亚型甲状腺乳头状癌 经典型甲状腺乳头状癌 临床病理特征 蛋白质组学 

分 类 号：R736.1[医药卫生—肿瘤]