摘要
目的 分析肝细胞癌组织及配对癌旁组织的蛋白质组数据,筛选与肝细胞癌患者预后相关的生物标志物.方法 通过对5组肝细胞癌组织及配对癌旁组织进行定量蛋白质组学测序,利用差异分析筛选出差异表达蛋白质.对差异表达蛋白质进行Gene Ontology(GO)功能注释和Kyoto encyclopedia of genes and genomes(KEGG)通路分析.同时,利用公共数据库和组织芯片对预后相关的差异表达蛋白质进行筛选与验证.结果 在肝细胞癌组织和癌旁组织间共筛选出差异表达蛋白质820个.相比癌旁组织,在肝细胞癌组织中上调的蛋白质有422个,下调的蛋白质有398个.GO功能注释和KEGG通路分析的结果表明差异表达蛋白质富集到细胞内重要的生物学过程、结构和信号通路.在mRNA和蛋白质水平上,BAG3在肝细胞癌组织中的表达水平显著高于正常肝组织,并且BAG3高表达与肝细胞癌患者较差的预后相关.BAG3高表达是肝细胞癌患者预后的独立危险因素.结论 BAG3高表达与肝细胞癌患者预后不良相关,BAG3可作为肝细胞癌患者的预后标志物.
Abstract
Objective Analyze proteomic data from hepatocellular carcinoma(HCC)tissues and adjacent non-tumor tissues to identify biomarkers associated with the prognosis of patients with HCC.Method Through quantitative proteomic sequencing of five sets of HCC tissues and adjacent non-tumor tissues,differentially expressed proteins were screened using differential analysis.These differentially expressed proteins were subjected to Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)pathway analysis.Additionally,the prognosis-related differentially expressed proteins were screened and validated uti-lizing public databases and tissue microarrays.Results A total of 820 differentially expressed proteins were identified between HCC tissues and adjacent non-tumor tissues.Compared with adjacent non-tumor tissues,422 proteins were upregulated and 398 proteins were downregulated in HCC tissues.The results of GO functional annotation demonstrated that,at the biological process level,the dif-ferentially expressed proteins were primarily involved in ribosomal biosynthesis,rRNA processing,and rRNA metabolism.In terms of cellular components,they were mainly associated with collagen-containing extracellular matrices,90S pre-ribosomes,and Golgi trans-port complexes.Regarding molecular functions,the proteins were predominantly engaged in collagen binding,ATP-dependent activities acting on DNA,and alterations in helicase activity.The results of the KEGG pathway analysis indicated that the differentially expressed proteins were primarily enriched in pathways such as carbon metabolism,fatty acid degradation,and pyruvate metabolism.At both mR-NA and protein levels,the expression of BAG3 was significantly higher in HCC tissues than in normal tissues.High BAG3 expression was associated with poor prognosis in patients with HCC and served as an independent risk factor for prognosis in patients with HCC.Conclusion High expression of BAG3 is associated with poor prognosis in patients with HCC,and BAG3 can serve as a prognostic marker for patients with HCC.