Zhang Fenglin, Liu Kexin, Ao Mengfan, Zhao Jiangang, Liao Xinghe, Li Ping, Chen Hao
Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Nanfang Hospital, Southern Medical University, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
Biol Proced Online. 2025 Jul 15;27(1):26. doi: 10.1186/s12575-025-00278-1.
Immunosenescence has lately become a focal point in oncology investigations. Nevertheless, its significance in pancreatic adenocarcinoma (PAAD) remains to be elucidated. This research sought to examine the predictive value and treatment implications of immunosenescence-related genes in PAAD. We use the public datasets from TCGA and GEO to extract clinicopathological factors and RNA-sequencing data. Differentially expressed genes (DEGs) were ascertained, and then molecular subtypes were classified by consensus clustering. Functional enrichment analysis using KEGG and GO, GSEA, survival analysis, and the design of an immunosenescence-linked risk signature using Lasso-Cox regression is part of the analytical approach. We used TIMER, TISCH, etc., to further elaborate its relationship with the tumor immune microenvironment. Drug sensitivity analysis is conducted using GSCA. The independent prognostic gene MAFF's expression was validated utilizing GEPIA2, real-time quantitative PCR (RT-qPCR), and western blot (WB). We identify two immunosenescence-associated subtypes of PAADwith distinct gene expression profiles and clinical outcomes. The creation of a risk signature model utilizing IMSRGs reveals three genes-NCAM1, SESN1, and MAFF-that are significantly correlated with overall survival. The elevated-risk cohort, as identified by the risk assessment metric, correlates with poorer survival rates. Additionally, we uncover an association between the risk indicator and the tumor milieu, encompassing immune cell infiltration patterns and drug sensitivity profiles. Our results and published data show that MAFF levels in pancreatic cancer tissues markedly exceeds that of normal tissues and have a bad effect on prognosis. The study identifies a prognostic gene signature for PAAD, revealing its potential in personalized medicine and immunotherapy, and highlights the role of immunosenescence in cancer treatment.
免疫衰老最近已成为肿瘤学研究的一个焦点。然而,其在胰腺腺癌(PAAD)中的意义仍有待阐明。本研究旨在探讨免疫衰老相关基因在PAAD中的预测价值和治疗意义。我们使用来自TCGA和GEO的公共数据集来提取临床病理因素和RNA测序数据。确定差异表达基因(DEG),然后通过一致性聚类对分子亚型进行分类。使用KEGG和GO进行功能富集分析、GSEA、生存分析以及使用Lasso-Cox回归设计免疫衰老相关风险特征是分析方法的一部分。我们使用TIMER、TISCH等进一步阐述其与肿瘤免疫微环境的关系。使用GSCA进行药物敏感性分析。利用GEPIA2、实时定量PCR(RT-qPCR)和蛋白质免疫印迹(WB)验证独立预后基因MAFF的表达。我们识别出PAAD的两种免疫衰老相关亚型,它们具有不同的基因表达谱和临床结局。利用免疫衰老相关基因创建的风险特征模型揭示了三个与总生存显著相关的基因——NCAM1、SESN1和MAFF。风险评估指标确定的高风险队列与较差的生存率相关。此外,我们发现风险指标与肿瘤微环境之间存在关联,包括免疫细胞浸润模式和药物敏感性谱。我们的结果和已发表的数据表明,胰腺癌组织中的MAFF水平明显超过正常组织,并且对预后有不良影响。该研究确定了PAAD的预后基因特征,揭示了其在个性化医疗和免疫治疗中的潜力,并突出了免疫衰老在癌症治疗中的作用。