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

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.

Epistemology of the Origin of Cancer II: Fibroblasts Are the First Cells to Undergo Neoplastic Transformation

“…While SUMO-1 decreases autophagy [148,149], it also significantly increases hypoxic cell stress [150], and induces the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) [149]. Collectively, this leads to microtubule polymerization and integrin clustering that will progress to lung cancer [151,152], glioblastoma [153], endometrial cancer [154], actinic cheilitis and lip carcinoma [155], liver cancer [156,157], gastric cancer [158] or pancreatic carcinoma [159]. SUMOylation is used by viruses to modify their own proteins [160,161], most notably by HPV [162], cytomegalovirus (CMV) [163) or Epstein-Barr virus (EBV) [164,165] to support their own replication.…”

SP140 inhibitor suppressing TRIM22 expression regulates glioma progress through PI3K/AKT signaling pathway

“…Altered expression or mutations in these proteins can influence gene regulation and potentially contribute to tumor development (Seeler et al., 1998; Yordy et al., 2004). A previous study demonstrated a significant association between high SP family member expression in pancreatic adenocarcinoma (PAAD) and unfavorable clinicopathological characteristics as well as a poor prognosis for patients with PAAD (Duan et al., 2023). SP110 and SP140 showed high rates of nonsynonymous mutations in head and neck squamous cell carcinoma (Chang et al., 2020).…”