PCBP1在胰腺癌中的临床价值及其对胰腺癌细胞生物学功能的影响

Clinical implications of PCBP1 in pancreatic cancer cells and its effect on biological function

目的探索聚(rC)结合蛋白1(PCBP1)在胰腺导管腺癌(PDAC)中的临床价值及对胰腺癌细胞功能的影响。方法通过GEPIA2、K-MPlotter、GENEMANIA、STRING、LinkedOmics数据库进行差异表达、预后分析、分子网络构建及潜在机制探索,使用胰腺癌细胞株ASPC-1和Panc-1进行PCBP1的功能实验及铁死亡相关蛋白谷胱甘肽过氧化物酶4(GPX4)和核因子样2(NRF2)表达变化检测。结果PCBP1在PDAC中表达显著上调(P<0.05),高表达PCBP1的患者无疾病生存差(Log-rankP<0.05),分层分析发现男性高PCBP1表达预后差(Log-rankP<0.05),低突变状态高PCBP1表达预后差(Log-rankP=0.026),分子互作网络发现PCBP1与聚(rC)结合蛋白3、剪接因子3a亚基2等基因,与异质核核糖核蛋白K、基本同源物增强子等蛋白存在相互作用,富集分析发现PCBP1可能参与到细胞凋亡、坏死性凋亡、程序性细胞死亡等途径,PCBP1表达下调后,细胞迁移、侵袭、增殖能力显著下降(所有P<0.05),GPX4和NRF2表达显著升高。结论PCBP1在PDAC中发挥癌基因作用并通过调控铁死亡通路而影响PDAC预后。

Objective To explore the clinical value of PCBPI in pancreatic ductal adenocarcinoma(PDAC)and its effect on the biological function of pancreatic cancer cells.Methods(1)Differential ex-pression,prognostic analysis,molecular network construction,and potential mechanism exploration were performed using GEPIA2,K-M Plotter,GENEMANIA,STRING,and LinkedOmics databases.(2)The functional experiments of PCBP1 were tested via pancreatic cancer cell lines ASPC-1 and Panc-1,and the expression of ferroptosis related proteins-glutathione peroxidase 4(GPX4)and nuclear factor-like 2(NRF2)-was detected.Results(1)PCBPI expression was significantly upregulated in PDAC(P<0.05);(2)Overexpression of PCBP was associated with poor disease-free survival in patients[Log-rank P=0.026,hazard ratio(HR)=4.55];(3)Stratified analysis showed that high PCBP1 expression in the male population and in low mutation load states indicated poor prognosis(Log-rank P=0.019,0.026);(4)Molecular interaction networks showed that PCBP1 interacted with genes such as PCBP3,SF3A2 and proteins such as HNRNPK,ERH;(5)Enrichment analysis revealed that PCBP1 may be involved in path-ways such as cell apoptosis,necrotic apoptosis,programmed cell death;(6)After downregulation of PCBPI expression,the migration,invasion,and proliferation ability of cells significantly decreased(all P<0.05),and the expression of CPX4 and NRF2 significantly increased.Conclusion PCBP1 plays an oncogene role in PDAC and affects the prognosis of PDAC by regulating the ferroptosis pathway.