Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer
Abstract Ferroptosis plays a role in tumorigenesis by affecting lipid peroxidation and metabolic pathways; however, its prognostic or therapeutic relevance in pancreatic adenocarcinoma (PAAD) remains poorly understood. In this study, we developed a prognostic ferroptosis-related gene (FRG)-based ris...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-84607-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559705355288576 |
|---|---|
| author | Ting Ting Chung Zanyue Piao Seung Jin Lee |
| author_facet | Ting Ting Chung Zanyue Piao Seung Jin Lee |
| author_sort | Ting Ting Chung |
| collection | DOAJ |
| description | Abstract Ferroptosis plays a role in tumorigenesis by affecting lipid peroxidation and metabolic pathways; however, its prognostic or therapeutic relevance in pancreatic adenocarcinoma (PAAD) remains poorly understood. In this study, we developed a prognostic ferroptosis-related gene (FRG)-based risk model using cohorts of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), proposing plausible therapeutics. Differentially expressed FRGs between tumors from TCGA-PAAD and normal pancreatic tissues from Genotype-Tissue Expression were analyzed to construct a prognostic risk model using univariate and multivariate Cox regression and LASSO analyses. A model incorporating AURKA, CAV1, and PML gene expression effectively distinguished survival differences between high- and low-risk groups among TCGA-PAAD patients, with validation in two ICGC cohorts. The high-risk group was enriched in gene sets involving mTOR, MAPK, and E2F signaling. The immune and stromal cells infiltration score did not differ between the groups. Analysis of PRISM datasets using our risk model to classify pancreatic cell lines suggested the dasatinib’s efficacy in the high-risk group, which was experimentally confirmed in four cell lines with a high- or low-risk signature. In conclusion, this study proposed a robust FRG-based prognostic model that may help stratify PAAD patients with poor prognoses and select potential therapeutic avenues. |
| format | Article |
| id | doaj-art-f92f391372c14dbb9acaf113b3a86c14 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f92f391372c14dbb9acaf113b3a86c142025-01-05T12:17:20ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84607-6Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancerTing Ting Chung0Zanyue Piao1Seung Jin Lee2College of Pharmacy, Chungnam National UniversityCollege of Pharmacy, Chungnam National UniversityCollege of Pharmacy, Chungnam National UniversityAbstract Ferroptosis plays a role in tumorigenesis by affecting lipid peroxidation and metabolic pathways; however, its prognostic or therapeutic relevance in pancreatic adenocarcinoma (PAAD) remains poorly understood. In this study, we developed a prognostic ferroptosis-related gene (FRG)-based risk model using cohorts of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), proposing plausible therapeutics. Differentially expressed FRGs between tumors from TCGA-PAAD and normal pancreatic tissues from Genotype-Tissue Expression were analyzed to construct a prognostic risk model using univariate and multivariate Cox regression and LASSO analyses. A model incorporating AURKA, CAV1, and PML gene expression effectively distinguished survival differences between high- and low-risk groups among TCGA-PAAD patients, with validation in two ICGC cohorts. The high-risk group was enriched in gene sets involving mTOR, MAPK, and E2F signaling. The immune and stromal cells infiltration score did not differ between the groups. Analysis of PRISM datasets using our risk model to classify pancreatic cell lines suggested the dasatinib’s efficacy in the high-risk group, which was experimentally confirmed in four cell lines with a high- or low-risk signature. In conclusion, this study proposed a robust FRG-based prognostic model that may help stratify PAAD patients with poor prognoses and select potential therapeutic avenues.https://doi.org/10.1038/s41598-024-84607-6Pancreatic adenocarcinomaFerroptosisPrognosisAurora kinase ACaveolin 1Promyelocytic leukemia |
| spellingShingle | Ting Ting Chung Zanyue Piao Seung Jin Lee Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer Scientific Reports Pancreatic adenocarcinoma Ferroptosis Prognosis Aurora kinase A Caveolin 1 Promyelocytic leukemia |
| title | Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| title_full | Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| title_fullStr | Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| title_full_unstemmed | Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| title_short | Identification of ferroptosis-related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| title_sort | identification of ferroptosis related signature predicting prognosis and therapeutic responses in pancreatic cancer |
| topic | Pancreatic adenocarcinoma Ferroptosis Prognosis Aurora kinase A Caveolin 1 Promyelocytic leukemia |
| url | https://doi.org/10.1038/s41598-024-84607-6 |
| work_keys_str_mv | AT tingtingchung identificationofferroptosisrelatedsignaturepredictingprognosisandtherapeuticresponsesinpancreaticcancer AT zanyuepiao identificationofferroptosisrelatedsignaturepredictingprognosisandtherapeuticresponsesinpancreaticcancer AT seungjinlee identificationofferroptosisrelatedsignaturepredictingprognosisandtherapeuticresponsesinpancreaticcancer |