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一个用于预测胰腺癌患者预后的 E3 泛素-蛋白酶体基因特征。

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

机构信息

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Front Immunol. 2024 Jan 18;14:1332626. doi: 10.3389/fimmu.2023.1332626. eCollection 2023.

DOI:10.3389/fimmu.2023.1332626
PMID:38304253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10830689/
Abstract

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, 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 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.

摘要

胰腺癌是全球第七大癌症死因，其对放疗和化疗具有显著的耐药性。鉴定预后标志物和新型预后标志物将有助于患者分层和个体化精准治疗策略的制定。在本研究中，我们使用 TCGA-PAAD 筛选预后 E3 泛素连接酶并建立预后特征，使用 GEO 数据库验证预后特征的准确性。我们通过功能分析、实验和临床队列研究分析了靶基因的功能和预后疗效。我们开发了一个基于 9 个基因的 E3 连接酶的特征和列线图，并证明该特征能够准确预测胰腺癌患者的预后。WDR37 可能是胰腺癌中最具预后意义的 E3 泛素连接酶，临床队列分析表明其具有肿瘤抑制作用。功能分析和实验结果表明，WDR37 可能通过促进 TCP1 复合物的降解来抑制肿瘤并增加免疫细胞浸润。基于 E3 连接酶的特征可以准确预测胰腺癌患者的预后，因此可作为指导胰腺癌患者治疗的决策工具。同时，E3PMP 特征中的主要基因 WDR37 可作为治疗胰腺癌最具预后意义的 E3 泛素连接酶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/1b207f380f3e/fimmu-14-1332626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/0e81e47f1e60/fimmu-14-1332626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/d95efe346ed7/fimmu-14-1332626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/6b3e2aa09655/fimmu-14-1332626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/da57975f9f76/fimmu-14-1332626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/d078308a4d69/fimmu-14-1332626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/1b207f380f3e/fimmu-14-1332626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/0e81e47f1e60/fimmu-14-1332626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/d95efe346ed7/fimmu-14-1332626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/6b3e2aa09655/fimmu-14-1332626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/da57975f9f76/fimmu-14-1332626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/d078308a4d69/fimmu-14-1332626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f5/10830689/1b207f380f3e/fimmu-14-1332626-g006.jpg

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