Dataset Information

A Prognostic Model of Pancreatic Cancer Based on Ferroptosis-Related Genes to Determine Its Immune Landscape and Underlying Mechanisms.

ABSTRACT: Pancreatic cancer is one of the malignant tumors with the worst prognosis in the world. As a new way of programmed cell death, ferroptosis has been proven to have potential in tumor therapy. In this study, we used the TCGA-PAAD cohort combined with the previously reported 60 ferroptosis-related genes to construct and validate the prognosis model and in-depth analysis of the differences in the function and immune characteristics of different RiskTypes. The results showed that the six-gene signature prognostic model that we constructed has good stability and effectiveness. Further analysis showed that the upregulated genes in the high-risk group were mainly enriched in extracellular matrix receptor-related pathways and other tumor-related pathways and the infiltration of immune cells, such as B, T, and NK cells, was suppressed. In short, our model shows good stability and effectiveness. Further studies have found that the prognostic differences between different RiskTypes may be due to the changes in the ECM-receptor pathway and activation of the immune system. Additionally, ICI drugs can treat pancreatic cancer in high-risk groups.

SUBMITTER: Yu X

PROVIDER: S-EPMC8606410 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Prognostic Model of Pancreatic Cancer Based on Ferroptosis-Related Genes to Determine Its Immune Landscape and Underlying Mechanisms.

Yu Xiao X Zheng Qingyuan Q Zhang Menggang M Zhang Qiyao Q Zhang Shuijun S He Yuting Y Guo Wenzhi W

Frontiers in cell and developmental biology 20211108

Pancreatic cancer is one of the malignant tumors with the worst prognosis in the world. As a new way of programmed cell death, ferroptosis has been proven to have potential in tumor therapy. In this study, we used the TCGA-PAAD cohort combined with the previously reported 60 ferroptosis-related genes to construct and validate the prognosis model and in-depth analysis of the differences in the function and immune characteristics of different RiskTypes. The results showed that the six-gene signatu ...[more]

PMID: 34820374

Similar Datasets

Project description:Pancreatic cancer remains to have a high mortality, which is partly due to the lack of effective treatment strategies. In this study, genes with potential associations with immunophenotyping of pancreatic cancer were screened through bioinformatics analysis and the correlation between immune-related genes and the prognosis of pancreatic cancer patients was assessed. Firstly, differentially expressed immune genes were extracted from the pancreatic cancer-related datasets obtained for purposes of this study. The samples were processed by the "Consensus Cluster Plus" R package to determine the number of immune subtypes. Then, the pancreatic cancer immunophenotyping-related gene modules were determined. Differential analysis of immune gene modules was performed, and the function of genes related to pancreatic cancer immune subtypes was identified. The number of immune cells in the samples was calculated, followed by the differential expression analysis of immune cell numbers in each immune subtype of pancreatic cancer. The immune infiltration score was also estimated, and the correlation between the immune infiltration score and the patient prognosis with different immune subtypes was determined. Gene differences between each immune subtype were identified by differential expression analysis, and key immune genes affecting immunophenotyping were obtained. Following the analysis, 426 immune-related genes were identified to have potential involvement in the occurrence and development of pancreatic cancer, of which CD19 may be the most critical gene affecting the immunophenotyping of pancreatic cancer. CD19 played a significant role in the occurrence and development of IS2 and IS3 immune subtypes of pancreatic cancer through its action on B cells and T cells. Moreover, the expression of CD19 was increased in the collected pancreatic cancer tissues. Overall, our findings uncovered the critical role of CD19 in the prognosis of pancreatic cancer patients.

Project description:BackgroundGastrointestinal adenocarcinomas (GIACs) are common malignant tumors with poor prognosis in the world. Ferroptosis, characterized by the accumulation of intracellular iron and lipid reactive oxygen species, emerges as a pivotal process in tumorigenesis and cancer advancement. However, the implications of ferroptosis-related genes in GIAC remain to be elucidated. This study aimed at exploring the potential role of ferroptosis-related genes on the prognosis and treatment of GIAC.MethodsIn our study, comprehensive clinical, transcriptomic, and/or genomic data were acquired from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC), and Gene Expression Omnibus (GEO). We formulated a ferroptosis-score within the TCGA cohort through gene set variation analysis (GSVA) and subsequently validated in 4 GEO datasets (GSE84437, GSE17536, GSE103479, and GSE19417). Drug sensitivity and immunotherapy efficacy were analyzed in the GDSC dataset and the PRJEB25780 cohort, respectively.ResultsThe ferroptosis-score was significantly associated with favorable overall survival both in the training cohort [TCGA: P=0.003; hazard ratio (HR), 0.67, 95% confidence interval (95% CI): 0.52-0.87] and across the four validation cohorts (GSE17536: P=0.03; HR, 0.57, 95% CI: 0.34-0.96; GSE19417: P=0.047; HR, 0.53, 95% CI: 0.28-1.01; GSE84437: P=0.004; HR, 0.68, 95% CI: 0.51-0.90; GSE103479: P=0.03; HR, 0.55, 95% CI: 0.32-0.96). Furthermore, the ferroptosis-score was correlated with activation of the DNA damage repair pathway and resistance to cisplatin. Notably, GIACs with low ferroptosis-scores exhibited heightened expression of immune checkpoint molecules such as programmed death-(ligand) 1 and cytotoxic T lymphocyte antigen-4, elevated densities of tumor-infiltrating CD8+ T cells, and a favorable response to pembrolizumab monotherapy.ConclusionsOur findings delineated the clinical relevance of ferroptosis-related genes in GIACs and demonstrated the potential utility of the ferroptosis-score in predicting prognosis and immunotherapy effectiveness.

Project description:It is reported that ferroptosis has close relation with tumorigenesis and drug resistance. However, the clinical significance of ferroptosis in lung adenocarcinoma (LUAD) remains elusive, and the potential targets for ferroptosis-based treatment are limited. In this study, we constructed a 15-gene prognostic signature predicting overall survival based on ferroptosis-related genes (ferroptosis driver genes VDAC2, GLS2, FLT3, TLR4, PHKG2, phosphogluconate dehydrogenase (PGD), PANX1, KRAS, PEBP1, ALOX15, and ALOX12B, and suppressor genes ACSL3, CISD1, FANCD2, and SLC3A2) in The Cancer Genome Atlas (TCGA)-LUAD cohort. The signature's predictive ability was validated in the GSE68465 and GSE72094 cohorts by survival analysis and independent prognostic analysis with clinical features. Nomograms were provided for clinical reference. Functional analysis revealed that ferroptosis was closely related to cell cycle, cell metabolism, and immune pathways. Pan-cancer analysis comprehensively analyzed these 15 genes in 33 cancer types, indicating that the heterogeneity of 15 genes was evident across different cancer types. Besides, these genes were critical regulators modulating drug resistance, tumor microenvironment infiltration, and cancer stemness. Then, we screened 10 genes (TLR4, PHKG2, PEBP1, GLS2, FLT3, ALOX15, ACSL3, CISD1, FANCD2, and SLC3A2) as potential targets for further research because their biological functions in ferroptosis were consistent with their prognostic significance. Somatic mutation and copy number variation analysis revealed that the alteration rates of KRAS, PGD, and ALOX15 were more than 1% and significantly associated with overall survival in LUAD. Moreover, the expression of KRAS and PGD was positively related to tumor mutation burden, indicating that KRAS and PGD could serve as novel biomarkers for predicting immunotherapy response rate. Our study identified and validated a ferroptosis-related gene signature for LUAD, provided a 10-gene set for future research, and screened KRAS and PGD as potential novel immunotherapy biomarkers.

Dataset Information

A Prognostic Model of Pancreatic Cancer Based on Ferroptosis-Related Genes to Determine Its Immune Landscape and Underlying Mechanisms.

Publications

A Prognostic Model of Pancreatic Cancer Based on Ferroptosis-Related Genes to Determine Its Immune Landscape and Underlying Mechanisms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets