ATP结合盒转运蛋白A5在胰腺癌中的预后意义的生物信息学分析与验证

背景与目的 ATP结合盒（ABC）转运蛋白家族的成员ABCA5在多种肿瘤中发挥着重要的作用。然而，ABCA5在胰腺癌中的研究尚不清楚。因此，本研究通过生物信息学分析及临床样本验证，探讨ABCA5在胰腺癌中的表达及与患者预后的关系，同时对ABCA5在胰腺癌中的可能作用机制进行分析。方法 使用TCGA和GEO数据库，分析ABCA5在胰腺癌组织及正常组织中的表达情况，并用Kaplan-Meier方法绘制生存曲线，Cox比例风险模型进行单因素与多因素分析。采用免疫组织化学法检测65例胰腺癌组织和癌旁组织中ABCA5的表达，并分析其与预后及胰腺癌临床病理特征的关系。使用TIMER、STRING和Gene MANIA数据库对ABCA5与免疫细胞浸润、蛋白互相作用网络（PPI）和基因-基因互作网络进行分析。利用基因富集分析（GSEA）和相关性分析对ABCA5在胰腺癌中可能参与的信号通路及其可能的作用机制进行探索。通过癌症药物敏感性基因组学（GDSC）分析ABCA5与治疗药物敏感性的关系。结果 在TCGA和GEO数据集中，ABCA5在胰腺癌组织中的表达明显低于正常组织（均P<0.05）。在TCGA和GSE62452数据集中，ABCA5低表达的患者生存时间明显缩短（均P<0.05）；ABCA5的表达是胰腺癌患者预后的独立影响因素（HR=0.458，P=0.001；HR=0.439，P=0.017）。65例临床病例分析显示，ABCA5在癌组织与癌旁组织相比处于低表达水平，且ABCA5低表达患者的预后更差（均P<0.05），单因素与多因素Cox回归分析表明ABCA5的表达是胰腺癌患者预后的独立影响因素（HR=0.327，P=0.032）。TIMER数据库结果显示，ABCA5表达与免疫浸润密切相关。PPI蛋白互作网络显示，有14个与ABCA5相关的互作蛋白；基因-基因互作关系网络图得到20个与ABCA5相关的互作基因。基因富集分析与相关性分析结果显示，ABCA5在胰腺癌中可能与细胞周期和铁死亡有关。ABCA5高表达患者对5种治疗药物的IC₅₀明显低于ABCA5低表达患者（均P<0.05）。结论 ABCA5在胰腺癌组织中低表达并与患者不良预后相关，其表达水平是胰腺癌患者预后的独立影响因素，ABCA5在胰腺癌中的作用机制可能与细胞周期、免疫调节和铁死亡有关。

Bioinformatics analysis and validation of the prognostic significance of ATP-binding cassette transporter A5 in pancreatic cancer

Background and Aims ATP-binding cassette transporter A5 (ABCA5), a member of the ABC transporter, plays a crucial role in various cancers. However, the role of ABCA5 in pancreatic cancer remains unclear. Therefore, this study was conducted to explore the expression of ABCA5 in pancreatic cancer and its relationship with prognosis of patients, using both bioinformatics analysis and clinical sample validation. Additionally, the potential mechanisms of ABCA5 in pancreatic cancer were analyzed.Methods The expression of ABCA5 in pancreatic cancer tissues and normal tissues was analyzed using TCGA and GEO databases. Kaplan-Meier survival curves and Cox proportional hazards models were used for univariate and multivariate analyses of the survival of patients. Immunohistochemistry was employed to detect ABCA5 expression in 65 pancreatic cancer and adjacent tissue samples, and its association with prognosis and clinicopathologic features was assessed. TIMER, STRING, and Gene MANIA databases were used to analyze ABCA5 in relation to immune cell infiltration, protein-protein interaction networks (PPI), and gene-gene interaction networks. Gene set enrichment analysis (GSEA) and correlation analysis were performed to explore the potential signaling pathways and mechanisms involving ABCA5 in pancreatic cancer. The relationship between ABCA5 and drug sensitivity was analyzed using the Genomics of Drug Sensitivity in Cancer (GDSC).Results In both TCGA and GEO datasets, ABCA5 expression was significantly lower in pancreatic cancer tissues compared to normal tissues (both P<0.05); patients with low ABCA5 expression had significantly shorter overall survival in both TCGA and GSE62452 datasets (both P<0.05); ABCA5 expression was identified as an independent prognostic factor for pancreatic cancer patients (HR=0.458, P=0.001; HR=0.439, P=0.017). Clinical analysis of 65 cases revealed that ABCA5 was downregulated in cancer tissues compared to adjacent tissues, and patients with low ABCA5 expression had worse prognoses (both P<0.05). Univariate and multivariate Cox regression analyses indicated that ABCA5 expression was an independent prognostic factor for pancreatic cancer patients (HR=0.327, P=0.032). TIMER database results showed a close association between ABCA5 expression and immune infiltration. The PPI network revealed 14 interacting proteins associated with ABCA5, while the gene-gene interaction network identified 20 interacting genes. Gene enrichment and correlation analyses suggested that ABCA5 may be related to the cell cycle and ferroptosis in pancreatic cancer. Patients with high ABCA5 expression showed significantly lower IC₅₀ values for five therapeutic drugs than those with low ABCA5 expression (all P<0.05).Conclusion The expression of ABCA5 is downregulated in pancreatic cancer tissue and is associated with poor prognosis in patients. ABCA5 expression is an independent prognostic factor for pancreatic cancer, and its potential mechanism in pancreatic cancer may involve the cell cycle, immune regulation, and ferroptosis.