Development and validation of a ferroptosis-related prognostic model in pancreatic cancer

• DOI: 10.1007/s10637-021-01114-5
• Publication Date: 2021-06-30T23:34:32Z
• Authors: Chen-jie Qiu; Xue-bing Wang; Zi-ruo Zheng; Chao-zhi Yang; Kai Lin; Kai Zhang; Min Tu; Kui-rong Jiang; Wen-tao Gao
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Macrophages; CD8-Positive T-Lymphocytes; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; Nomograms; 03 medical and health sciences; Risk Factors; Transforming Growth Factor beta; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Ferroptosis; Humans

Abstract Background: The purpose of this study was to identify ferroptosis-related genes (FRGs) associated with the prognosis of pancreatic cancer and to construct a prognostic model based on FRGs. Methods: Based on pancreatic cancer data obtained from The Cancer Genome Atlas database, we established the prognostic model from 232 FRGs. A nomogram was constructed by combining the prognostic model and clinicopathological features. Gene Expression Omnibus datasets and tissue samples obtained from our center were utilized to validate the model. Relationship between risk score and immune cell infiltration was explored by CIBERSORT and TIMER.Results: The prognostic model was established based on four FRGs (ENPP2, ATG4D, SLC2A1 and MAP3K5) and can be an independent risk factor in pancreatic cancer (HR 1.648, 95% CI 1.335-2.035, p < 0.001). Based on the median risk score, patients were divided into a high-risk group and a low-risk group. The prognosis of the low-risk group was significantly better than that of the high-risk group. In the high-risk group, patients treated with chemotherapy had a better prognosis. The nomogram showed that the model was the most important element. Gene set enrichment analysis identified three key pathways, namely, TGFβ signaling, HIF signaling pathway and adherens junction. The prognostic model can also affect the immune cell infiltration, such as macrophages M0, M1, CD4+T cell and CD8+T cell. Conclusion: A ferroptosis-related prognostic model can be employed to predict the prognosis of pancreatic cancer. Ferroptosis can be an important marker and immunotherapy can be a potential therapeutic target for pancreatic cancer.