剪接因子SF3B4在肺腺癌肺内转移中高表达及其临床意义  

Clinical Significance of Splicing Factor SF3B4 Overexpression in Intrapulmonary Metastasis of Lung Adenocarcinoma

作　　者：余绍斌 张培培 肖寒 陈舒晨[1,2] YU Shaobin;ZHANG Peipei;XIAO Han;CHEN Shuchen(Department of Thoracic Surgery,Fujian Medical University Union Hospital,Fuzhou 350001,China;Key Laboratory of Gastrointestinal Cancer,Ministry of Education,School of Basic Medical Science,Fujian Medical University,Fuzhou 350122,China;Department of Pathology,Fujian Medical University Union Hospital,Fuzhou 350001,China)

机构地区：[1]福建医科大学附属协和医院胸外科,福州350001 [2]福建医科大学基础医学院消化道恶性肿瘤教育部重点实验室,福州350122 [3]福建医科大学附属协和医院病理科,福州350001

出　　处：《福建医科大学学报》2024年第6期367-376,共10页Journal of Fujian Medical University

基　　金：福建医科大学启航基金(2021QH1043)。

摘　　要：目的利用空间蛋白组学技术筛选肺腺癌肺内转移与多原发肺腺癌的差异蛋白,探讨剪接因子3B亚基4(SF3B4)的表达特征及其临床意义。方法采用空间蛋白组学技术分析肺腺癌样本中肿瘤细胞富集区域的蛋白质表达,结合生物信息学工具和数据库,对SF3B4在泛癌种中的表达模式及其与肺腺癌预后和肿瘤进展的相关性进行综合评估。结果共鉴定出8736种蛋白质,筛选出437种差异表达显著的蛋白质,SF3B4在肺内转移癌中上调最显著,与肺腺癌的高分期、分化及预后差密切相关。基因本体功能注释和京都基因与基因组百科全书功能分析揭示上调蛋白富集于糖酵解、碳代谢及核糖核蛋白复合体通路,而下调蛋白与细胞外基质重塑及结构分子活性相关。结论系统性筛选出与肺腺癌肺内转移相关的差异蛋白,确认SF3B4的高表达与不良预后、肿瘤进展及信号通路激活相关,为肺腺癌肺内转移的诊断和治疗提供新线索。Objective This study aims to identify differential proteins between pulmonary adenocarcinoma lung metastasis and multifocal pulmonary adenocarcinoma using spatial proteomics technology,and to explore the expression characteristics and clinical significance of the splicing factor 3B Subunit 4(SF3B4).Methods Spatial proteomics technology was employed to analyze protein expression in tumor cell-enriched regions of pulmonary adenocarcinoma samples,and bioinformatics tools and databases were used to comprehensively assess the expression pattern of SF3B4 across various cancers and its correlation with pulmonary adenocarcinoma prognosis and tumor progression.Results A total of 8736 proteins were identified,with differential analysis revealing 437 significantly differentially expressed proteins,among which SF3B4 was most prominently upregulated in lung metastasis and closely associated with high pulmonary adenocarcinoma stage,poor differentiation,and poor prognosis.Gene ontology and Kyoto encyclopedia of genes and genomes functional analyses indicated that upregulated proteins were enriched in glycolysis,carbon metabolism,and ribonucleoprotein complex pathways,while downregulated proteins were related to extracellular matrix remodeling and structural molecular activity.Conclusion This study systematically identified differential proteins associated with pulmonary adenocarcinoma lung metastasis for the first time,confirming that high expression of SF3B4 is correlated with poor prognosis,tumor progression,and activation of signaling pathways,providing new clues for the diagnosis and treatment of pulmonary adenocarcinoma lung metastasis.

关 键 词：肺腺癌 肺内转移 多原发肺腺癌 剪接因子SF3B4 空间蛋白组学 鉴别诊断 

分 类 号：R73[医药卫生—肿瘤]