泛素化相关基因（URGs）在多种人类疾病中起着关键作用，然而，它们与胰腺腺癌（PAAD）的关联尚未明确描述。我们旨在通过体外分析和实验证实，以全面了解URGs在PAAD中的贡献，并使用批量RNA测序和单细胞RNA测序数据确定一种强大的基于mRNA-lncRNA的分子预后面板，用于PAAD患者。首先，我们从TCGA平台收集了多组学数据，描述了泛癌中URGs的全面格局。此外，我们对PAAD进行了详尽分析。在正常细胞和恶性细胞之间检测到泛素化途径的激活和URGs的表达存在显著差异。无监督的分层聚类确定了两种具有不同临床结果、泛素化途径活性、免疫微环境和功能注释特征的PAAD亚型。通过在训练和验证数据集中利用泛素化相关mRNA和lncRNA的表达谱开发和验证了一个新的基于mRNA-lncRNA的泛素化相关预后面板，该面板具有满意的预测效能。我们的泛素化相关模型可作为一种有效的预后指数，并在评估PAAD患者的生存状况方面胜过其他四种公认的面板。通过深入研究肿瘤免疫微环境、突变负担和化疗反应，揭示了根据我们的面板预后差异的潜在机制。我们的发现还表明，法尼酰转移酶抑制剂FTI-277在高风险患者中具有更好的治疗效果，而Akt变构抑制剂MK-2206在低风险患者中具有更优越的治疗效果。实时PCR结果显示，在所有三种PAAD细胞系中，AC005062.1的RNA表达增加了数千倍。综上所述，基于URGs的分类面板可作为PAAD患者生存评估的预测工具，并且该面板中的基因可以成为PAAD治疗的潜在靶点。© 2023. 作者。

Ubiquitination-related genes (URGs) exerted a crucial part in a variety of human disease disorders; however, their association with pancreatic adenocarcinoma (PAAD) had yet to be clearly described. We aimed to comprehensively characterize the contributions of URGs in PAAD through in silico analysis and experimental validation, and then identified a robust mRNA-lncRNA-based molecular prognostic panel for patients with PAAD using bulk RNA-sequencing and single-cell RNA-sequencing data. Initially, we collected the multi-omics data from TCGA platform to depict a comprehensive landscape of URGs in pan-cancer. Furthermore, we were accurate to PAAD for in-depth analysis. Significant differences of the activation of ubiquitination pathways and the expression of URGs were detected between normal and malignant cells. Unsupervised hierarchical clustering determined two PAAD subtypes with distinct clinical outcomes, ubiquitination pathway activities, immune microenvironment, and functional annotation characteristics. The expression profiles of ubiquitination-associated mRNAs and lncRNAs in the training and validation datasets were utilized to develop and verify a novel ubiquitination-related mRNA-lncRNA prognostic panel, which had a satisfied prediction efficiency. Our ubiquitination-associated model could function as an effective prognostic index and outperformed four other recognized panels in evaluating PAAD patients' survival status. Tumor immune microenvironment, mutation burden, and chemotherapy response were intensively explored to demonstrate the underlying mechanism of prognostic difference according to our panel. Our findings also revealed that FTI-277, a farnesyltransferase inhibitor, had a better curative effect in high-risk patients, while MK-2206, an Akt allosteric inhibitor, had a superior therapeutic effect in low-risk patients. The real-time PCR results uncovered the RNA expression of AC005062.1 in all the three PAAD cell lines was elevated several thousandfold. In conclusion, our URGs-based classification panel could be triumphantly served as a prediction tool for survival evaluation in patients with PAAD, and the genes in this panel could be developed as a potential target in PAAD therapy.© 2023. The Author(s).