In:
Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-5-18)
Abstract:
Objective: Necroptosis represents a new target for cancer immunotherapy and is considered a form of cell death that overcomes apoptosis resistance and enhances tumor immunogenicity. Herein, we aimed to determine necroptosis subtypes and investigate the roles of necroptosis in pancreatic cancer therapy. Methods: Based on the expression of prognostic necroptosis genes in pancreatic cancer samples from TCGA and ICGC cohorts, a consensus clustering approach was implemented for robustly identifying necroptosis subtypes. Immunogenic features were evaluated according to immune cell infiltrations, immune checkpoints, HLA molecules, and cancer–immunity cycle. The sensitivity to chemotherapy agents was estimated using the pRRophetic package. A necroptosis-relevant risk model was developed with a multivariate Cox regression analysis. Results: Five necroptosis subtypes were determined for pancreatic cancer (C1∼C5) with diverse prognosis, immunogenic features, and chemosensitivity. In particular, C4 and C5 presented favorable prognosis and weakened immunogenicity; C2 had high immunogenicity; C1 had undesirable prognosis and high genetic mutations. C5 was the most sensitive to known chemotherapy agents (cisplatin, gemcitabine, docetaxel, and paclitaxel), while C4 displayed resistance to aforementioned agents. The necroptosis-relevant risk model could accurately predict prognosis, immunogenicity, and chemosensitivity. Conclusion: Our findings provided a conceptual framework for comprehending necroptosis in pancreatic cancer biology. Future work is required for evaluating its relevance in the design of combined therapeutic regimens and guiding the best choice for immuno- and chemotherapy.
Type of Medium:
Online Resource
ISSN:
1663-9812
DOI:
10.3389/fphar.2022.862502
DOI:
10.3389/fphar.2022.862502.s001
DOI:
10.3389/fphar.2022.862502.s002
DOI:
10.3389/fphar.2022.862502.s003
DOI:
10.3389/fphar.2022.862502.s004
DOI:
10.3389/fphar.2022.862502.s005
DOI:
10.3389/fphar.2022.862502.s006
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2587355-6
SSG:
15,3
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