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

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.

Pancreatic adenocarcinoma associated immune-gene signature as a novo risk factor for clinical prognosis prediction in hepatocellular carcinoma

“…Compared with them, our model had outstanding general applicability with high accuracy and stability. As to the miRNA or lncRNA-related signatures 65 , 69 – 71 , our PAAD-IRGS was more stable and convinced; Compared with multiple-gene signatures 9 , 68 , necroptosis-related gene signature 72 and m6A-related gene signature 73 , 74 , which had been reported, our PAAD-IRGS was new and more versatile with outstanding performance. It can be well applied to prognostic prediction of multiple cancers with different prognostic parameters.…”

Identification and Validation of Prognosis-Related Necroptosis Genes for Prognostic Prediction in Hepatocellular Carcinoma

“…Recently, its characteristics have been described in a variety of human tumors. Generally, according to different subtypes of necroptosis, the prognosis of patients can be accurately predicted [ 6 , 7 ]. In hepatocellular carcinoma, it has been recognized that necroptosis is a double-edged sword that provides the inflammatory environment required for carcinogenesis, while the immune response is launched to fight against tumors [ 17 ].…”

“…On the other hand, inflammatory responses caused by cytokines released by necrotic cells can promote the development of tumors [ 4 , 5 ]. Recently, a prognosis-related necroptosis gene signature was used to predict the prognosis and describe the immune microenvironment in human tumors [ 6 , 7 ].…”

Characterization of Necroptosis-Related Molecular Subtypes and Therapeutic Response in Lung Adenocarcinoma

“…Different from cellular apoptosis, necroptosis has been recognized as a specially programmed cell death with an essential role in maintaining the stabilization of the internal environment and participating in the pathogenesis of multiple diseases including various infections, tumor formation, and autoimmune diseases ( Schreiber et al, 2017 ; Wang et al, 2019 ; Xia et al, 2020 ). Increasing studies have identified necroptosis-related gene signatures and subtypes to predict the prognosis and therapeutic response of multiple tumors including breast cancer ( Chen W. et al, 2022 ), kidney renal clear cell carcinoma ( Chen W. et al, 2022 ), and pancreatic adenocarcinoma ( Wu et al, 2022 ), but there is no research focusing on the relationships between NRGs and LUAD.…”