泛癌分析揭示SPP1与多种肿瘤的临床预后相关性  

Pan-cancer analysis revealed the correlation between SPP1 and clinical prognosis of multiple tumors

作　　者：陈洁 张默[3] 门展宇 陈琳 汪露[2,4] 庞晓丛 CHEN Jie;ZHANG Mo;MEN Zhan-yu;CHEN Lin;WANG Lu;PANG Xiao-cong(School of Pharmacy,Xuzhou Medical University,Xuzhou 221009,Jiangsu Province,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Department of Integrated Western and Chinese Medicine,Peking University First Hospital,Beijing 100034,China;Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;School of Chemical and Materials Engineering,Hainan Vocational University of Science and Technology,Haikou 571137,Hainan Province,China)

机构地区：[1]徐州医科大学药学院,江苏徐州221009 [2]北京大学第一医院临床药理研究所,北京100034 [3]北京大学第一医院中西医结合科,北京100034 [4]北京大学第一医院药学部,北京100034 [5]海南科技职业大学化学与材料工程学院,海南海口571137

出　　处：《中国临床药理学杂志》2024年第12期1827-1831,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划资助项目(2020YFC2008304);国家自然科学基金面上基金资助项目(82274015)。

摘　　要：目的通过生物信息学方法分析分泌性磷酸蛋白(SPP1)在肿瘤中的功能作用,评估在人类泛癌中的差异表达和预后价值。方法癌症样本数据来自the Cancer Genome Atlas(TCGA)、Genetype-tissue Expression(GTEx)数据库,利用CPTAC数据库研究SPP1在泛癌中的基因差异表达,利用GEPIA2数据库研究SPP1与患者生存预后之间的相关性,利用CbioPortal工具评估SPP1在32种肿瘤中的基因突变改变形式。结果在32种肿瘤类型中,SPP1 mRNA表达在8种癌症中有差异,仅在肾透明细胞癌中蛋白表达下降,其余癌症中蛋白表达均增加,基因的表达在肿瘤分期中具有特异性;SPP1 mRNA的表达与患者的总生存期(OS)和无病生存期(DFS)呈负相关;SPP1在肿瘤中的基因活性与低甲基化相关,即低甲基化可以激活致癌基因进而影响肿瘤细胞的生成、凋亡、增生,进一步影响肿瘤的发生发展;SPP1以错义突变为主要基因突变形式,基因的改变与前列腺癌、胃癌患者较差的预后相关。结论基于泛癌分析成功验证了SPP1在人类癌症中的特异性,特异性表达与癌症患者的临床预后紧密相关,说明SPP1可以作为癌症预后的靶点。Objective This study utilized bioinformatics to investigate the role of secreted phosphoprotein 1(SPP1)in tumors and assess its differential expression and prognostic significance across human cancers.Method Cancer sample data was sourced from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database.Analysis of gene expression differences in pan-cancer involving SPP1utilized the CPTAC database,correlations between SPP1 and patient survival outcomes were assessed using GEPIA2,and alterations in gene mutations for SPP1 across 32 cancers were appraised via the CbioPortal tool.Results Across 32 tumor types,SPP1 mRNA disparity is observed in eight cancer types,decreasing only in clear cell renal carcinoma while increasing in other malignancies.Expression in tumor stage is specific;SPP1 mRNA negatively correlates with patient overall survival(OS)and disease-free survival(DFS);low methylation associated with SPP1gene activity promotes oncogene activation,impacting tumor cell generation,apoptosis,and proliferation,thereby influencing cancer progression;SPP1 primarily exhibits missense mutations that correlate with poor prognoses in prostate and stomach cancer patients.Conclusion Through pan-cancer studies,SPP1's selective expression in human malignancies was validated and found to be strongly correlated with clinical prognosis.This suggests that SPP1 is a viable target for cancer prognostic precision.

关 键 词：分泌性磷酸蛋白 预后 DNA甲基化 基因突变 泛癌分析 

分 类 号：R979.1[医药卫生—药品]