Table8_Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma.XLSX

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

背景：胰腺腺癌（Pancreatic adenocarcinoma, PAAD）恶性程度高、预后极差，患者5年总生存率仅约7%。为改善PAAD患者的预后，亟需对其发病机制开展更全面深入的研究，并挖掘新型诊断标志物与治疗靶点。越来越多的研究证据表明，小泛素样修饰因子（small ubiquitin-like modifier, SUMO）家族与多种癌症的发生发展密切相关。然而，SUMO家族在PAAD中的功能尚不明确，相关研究亦十分匮乏。
方法：本研究采用R语言、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。
结果：研究发现，SUMO家族成员在PAAD中呈高表达状态，且其高表达与PAAD患者不良的临床病理特征及不良预后显著相关。此外，SUMO家族成员与M6A甲基化调控因子、多种致癌基因存在显著共表达关系，并在包括上皮间质转化（Epithelial-Mesenchymal Transition, EMT）在内的多条致癌通路中发挥激活作用。值得关注的是，SUMO家族成员与TP53突变状态的紧密关联，以及SUMO1/2对PAAD免疫的负向调控作用，或可阐明SUMO家族促进PAAD发生发展的潜在机制。进一步而言，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表达水平与吉西他滨（gemcitabine）、紫杉醇（paclitaxel）、多柔比星（doxorubicin）等多种靶向或化疗药物敏感性的正相关关系，为该研究指明了未来的临床转化方向。
结论：综上，SUMO家族与PAAD的发生发展密切相关，可作为PAAD患者新型的生物标志物与治疗靶点。