基于4D-DIA蛋白质组学分析肺腺癌骨转移与非骨转移患者的血清差异蛋白  

Analysis of serum differential proteins in patients with bone metastases and non-bone metastases in lung adenocarcinoma based on 4D-DIA proteomics

作　　者：李茂琛 来学婷 张红霞 王布[2] 张志华[2] 张秀珑[2] LI Maochen;LAI Xueting;ZHANG Hongxia;WANG Bu;ZHANG Zhihua;ZHANG Xiulong(Graduate School of Hebei North University,Hebei Zhangjiakou 075000,China;The First Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075000,China)

机构地区：[1]河北北方学院研究生院,河北张家口075000 [2]河北北方学院附属第一医院,河北张家口075000

出　　处：《现代肿瘤医学》2024年第10期1824-1831,共8页Journal of Modern Oncology

基　　金：河北省医学科学研究课题计划(编号:20240476)。

摘　　要：目的:基于深度血液4D-DIA蛋白质组学分析,寻找肺腺癌骨转移组与非骨转移组的差异蛋白,为肺腺癌骨转移诊断治疗提供新线索。方法:采用4D-DIA蛋白质组学技术,纳入6例肺腺癌非骨转移(lung adenocarcinoma non-bone metastases, LUADNBM)及6例肺腺癌骨转移(lung adenocarcinoma bone metastasis, LUADBM)患者进行血清蛋白质组学分析。以表达倍数(fold change, FC)>1.5倍(上调大于1.5倍或下调小于0.67倍)且P值<0.05(T-test或其他)为标准,得到比较组间的上调、下调蛋白质数目。对两组间的可定量蛋白进行基因集富集分析(gene set enrichment analysis,GSEA)。应用String网站和R语言对差异蛋白进行主成分分析(principal component analysis,PCA)、基因本体论(gene ontology,GO)分析和KEGG(Kyoto encyclopedia of genes and genomes)通路数据库分析。结果:LUADNBM组与LUADBM组间比较发现2 585个可定量蛋白,其中18个差异蛋白。GSEA结果显示,可定量蛋白主要富集在真核翻译延伸阶段、SARS-CoV-2主要翻译机制通路(P<0.05)。PCA结果显示,差异蛋白可明显区分LUADNBM与LUADBM患者。GO分析结果表明,差异蛋白主要富集在高尔基管腔和细胞外基质,在皮肤硫酸盐蛋白聚糖的生物合成和代谢过程以及硫酸软骨素的分解代谢和生物合成中发挥重要作用;KEGG结果表明:上调蛋白主要富集在近端小管碳酸氢盐回收、胆汁分泌、N-聚糖生物合成、胰岛素分泌、醛固酮的合成和分泌等通路;下调蛋白主要富集在神经退行性疾病的途径,如阿尔茨海默病、亨廷顿病、帕金森病、脊髓小脑性共济失调等。结论:肺腺癌骨转移组与非骨转移组蛋白存在明显差异,通过发现新型蛋白标志物为早期筛查诊断骨转移提供新线索。Objective:To find the differential proteins between lung adenocarcinoma bone metastasis and adenocarcinoma non-bone metastasis based on deep blood 4D-DIA proteomic analysis,so as to provide a basis for diagnosis and treatment of lung adenocarcinoma bone metastasis.Methods:Serum proteomics analysis was performed in 6 patients with lung adenocarcinoma non-bone metastases(LUADNBM)and 6 patients with lung adenocarcinoma bone metastasis(LUADBM)using 4D-DIA proteomics.The expression fold(fold change,FC)was>1.5-fold(up-regulated by more than 1.5-fold or down-regulated by less than 0.67-fold)and P value<0.05(T-test or other)was used as the standard to obtain the number of up-regulated and down-regulated proteins between the comparison groups.Gene set enrichment analysis(GSEA)was performed on quantifiable proteins between different comparison groups.Principal component analysis(PCA),gene ontology(GO)analysis and KEGG(Kyoto encyclopedia of genes and genomes)pathway database were performed on the String website and R language.Results:A total of 2585 quantifiable proteins were found between the LUADNBM group and the LUADBM group,including 18 differential proteins.The results of GSEA showed that the quantified protein was mainly enriched in the eukaryotic translation extension stage and the main translation mechanism pathway of SARS-CoV-2(P<0.05).The results of PCA showed that the differential protein could clearly distinguish LUADNBM from LUADBM patients.The results of GO analysis showed that the differential proteins were mainly enriched in the lumen of the Golgi canal and extracellular matrix,and played an important role in the biosynthesis and metabolism of cutaneous sulfate proteoglycans and the catabolism and biosynthesis of chondroitin sulfate.The results of KEGG showed that the up-regulated proteins were mainly enriched in the pathways of proximal tubular bicarbonate recovery,bile secretion,N-glycan biosynthesis,insulin secretion,and aldosterone synthesis and secretion.Down-regulated proteins were mainly enriched in n

关 键 词：肺腺癌 骨转移 蛋白质组学 新型蛋白标志物 

分 类 号：R734.2[医药卫生—肿瘤]