Novel necroptosis-related gene signature for predicting the prognosis of pancreatic adenocarcinoma

Aging (Albany NY). 2022 Jan 24;14(2):869-891. doi: 10.18632/aging.203846. Epub 2022 Jan 24.

Abstract

Pancreatic adenocarcinoma (PAAD) is a deadly digestive system tumor with a poor prognosis. Recently, necroptosis has been considered as a type of inflammatory programmed cell death. However, the expression of necroptosis-related genes (NRGs) in PAAD and their associations with prognosis remain unclear. NRGs' prediction potential in PAAD samples from The TCGA and GEO datasets was investigated. The prediction model was constructed using Lasso regression. Co-expression analysis showed that gene expression was closely related to necroptosis. NRGs were shown to be somewhat overexpressed in high-risk people even when no other clinical symptoms were present, indicating that they may be utilized in a model to predict PAAD prognosis. GSEA showed immunological and tumor-related pathways in the high-risk group. Based on the findings, immune function and m6A genes differ significantly between the low-risk and high-risk groups. MET, AM25C, MROH9, MYEOV, FAM111B, Y6D, and PPP2R3A might be related to the oncology process for PAAD patients. Moreover, CASKIN2, TLE2, USP20, SPRN, ARSG, MIR106B, and MIR98 might be associated with low-risk patients with PAAD. NRGs and the relationship of the immune function, immune checkpoints, and m6A gene expression with NRGs in PAAD may be considered as potential therapeutic targets that should be further studied.

Keywords: TCGA and GEO datasets; bioinformatics analysis; immunity; m6A and immune checkpoint; necroptosis-related genes (NRGs); pancreatic adenocarcinoma (PAAD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / pathology
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs*
  • Necroptosis / genetics
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • Ubiquitin Thiolesterase / genetics

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • FAM111B protein, human
  • MIRN98 microRNA, human
  • MicroRNAs
  • USP20 protein, human
  • Ubiquitin Thiolesterase