Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma

Yunjie Duan; Yongxing Du; Yongrun Mu; Zongting Gu; Chengfeng Wang

doi:10.3389/fmolb.2022.1096679

Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma

Front Mol Biosci. 2022 Dec 15:9:1096679. doi: 10.3389/fmolb.2022.1096679. eCollection 2022.

Authors

Yunjie Duan¹, Yongxing Du¹, Yongrun Mu¹, Zongting Gu², Chengfeng Wang^{1

3}

Affiliations

¹ 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.
² Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
³ Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.

Abstract

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.

Keywords: M6A; SUMO family; TP53; biomarkers; immune infiltration; pancreatic adenocarcinoma; prognosis.