Duan Yunjie, Du Yongxing, Mu Yongrun, Gu Zongting, Wang Chengfeng
State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Front Mol Biosci. 2022 Dec 15;9:1096679. doi: 10.3389/fmolb.2022.1096679. eCollection 2022.
Pancreatic adenocarcinoma (PAAD) has a high degree of malignancy and a very poor prognosis, and the 5-year overall survival rate of patients is approximately 7%. To improve the prognosis of patients with PAAD, a more comprehensive and in-depth study of the pathogenesis of PAAD and the identification of new diagnostic markers and treatment targets are urgently needed. Increasing evidence supports that the small ubiquitin-like modifier (SUMO) family is closely related to the occurrence and development of a variety of cancers. However, the function of the SUMO family in PAAD is not clear, and related research is very scarce. R, Cytoscape, cBioPortal, and other software and online databases were used to comprehensively analyze the expression characteristics, prognostic value, and oncogenic mechanism of the SUMO family in PAAD. SUMO family members are highly expressed in PAAD, and high expression of SUMO family members is significantly associated with poor clinicopathological features and poor prognosis in PAAD patients. In addition, SUMO family members are significantly coexpressed with M6A methylation regulators and various oncogenes and play an activating role in various oncogenic pathways, including EMT. Furthermore, it is worth noting that the close association between SUMO family members and TP53 mutation status and the negative regulatory effect of SUMO1/2 on PAAD immunity may represent the potential mechanism by which SUMO family members promote the development of PAAD. Moreover, the coexpression characteristics of SUMO family members and a variety of cancer-promoting immune checkpoint genes, as well as the positive correlation between SUMO4 expression level and the sensitivity of various targeted or chemotherapeutic drugs, including gemcitabine, paclitaxel, and doxorubicin, suggest future clinical directions of this study. The SUMO family is closely related to the occurrence and development of PAAD and can be used as a new biomarker and therapeutic target for patients with PAAD.
胰腺腺癌（PAAD）具有高度恶性，预后极差，患者的5年总生存率约为7%。为改善PAAD患者的预后，迫切需要对PAAD的发病机制进行更全面深入的研究，并鉴定新的诊断标志物和治疗靶点。越来越多的证据支持小泛素样修饰物（SUMO）家族与多种癌症的发生发展密切相关。然而，SUMO家族在PAAD中的功能尚不清楚，相关研究非常匮乏。利用R、Cytoscape、cBioPortal等软件及在线数据库，全面分析SUMO家族在PAAD中的表达特征、预后价值及致癌机制。SUMO家族成员在PAAD中高表达，SUMO家族成员的高表达与PAAD患者不良的临床病理特征及预后显著相关。此外，SUMO家族成员与M6A甲基化调节因子及多种癌基因显著共表达，并在包括上皮-间质转化（EMT）在内的多种致癌途径中发挥激活作用。此外，值得注意的是，SUMO家族成员与TP53突变状态密切相关，且SUMO1/2对PAAD免疫具有负调节作用，这可能代表SUMO家族成员促进PAAD发展的潜在机制。此外，SUMO家族成员与多种促癌免疫检查点基因的共表达特征，以及SUMO4表达水平与包括吉西他滨、紫杉醇和阿霉素在内的多种靶向或化疗药物敏感性之间的正相关，提示了本研究未来的临床方向。SUMO家族与PAAD的发生发展密切相关，可作为PAAD患者的新型生物标志物和治疗靶点。
