DataSheet_1_An E3 ubiquitin-proteasome gene signature for predicting prognosis in patients with pancreatic cancer.xlsx

Pancreatic cancer is the seventh leading cause of cancer death worldwide, which is demonstrated with remarkable resistance to radiotherapy and chemotherapy. The identification of prognosis signature and novel prognostic markers will facilitate patient stratification and an individualized precision therapy strategy. In this study, TCGA-PAAD was used to screen prognostic E3 ubiquitin ligases and establish prognostic signatures, and GEO database was used to verify the accuracy of prognostic signatures. Functional analysis, in vitro experiments and clinical cohort studies were used to analyze the function and prognostic efficacy of the target gene. An E3 ligase-based signature of 9 genes and the nomogram were developed, and the signature was proved to accurately predict the prognosis of patients with pancreatic cancer. WDR37 might be the most prognostic E3 ubiquitin ligase in pancreatic cancer, and the clinical cohort analyses suggested a tumor‐suppressive role. The results of functional analysis and in vitro experiments indicated that WDR37 may promote the degradation of TCP1 complex to inhibit tumor and improve immune cell infiltration. The E3 ligase-based signature accurately predicted the prognosis of patients with pancreatic cancer, so it can be used as a decision-making tool to guide the treatment of patients with pancreatic cancer. At the same time, WDR37, the main gene in E3PMP signature, can be used as the most prognostic E3 ubiquitin ligase in the treatment of pancreatic cancer.

胰腺癌是全球范围内第七大癌症相关死亡病因，且对放疗与化疗均表现出显著的耐药性。预后特征与新型预后标志物的鉴定，将助力患者分层管理与个体化精准治疗策略的落地实施。本研究通过TCGA-PAAD数据集筛选预后相关E3泛素连接酶（E3 ubiquitin ligase）并构建预后特征模型，同时利用GEO数据库验证该预后特征的准确性。本研究通过功能富集分析、体外实验及临床队列研究，对目标基因的功能与预后效能展开分析。本研究构建了一个包含9个E3连接酶的预后特征模型及列线图（nomogram），并证实该模型可精准预测胰腺癌患者的预后情况。WDR37可能是胰腺癌中最具预后价值的E3泛素连接酶，临床队列分析提示其发挥抑癌作用。功能分析与体外实验结果表明，WDR37或可通过促进TCP1复合物（TCP1 complex）的降解以抑制肿瘤进展，并改善肿瘤微环境中的免疫细胞浸润。该基于E3连接酶的预后特征模型可精准预测胰腺癌患者的预后，因此可作为指导胰腺癌患者临床治疗的决策工具。同时，作为E3PMP特征中的核心基因，WDR37可作为胰腺癌治疗中最具预后价值的E3泛素连接酶。