期刊
ANNALS OF TRANSLATIONAL MEDICINE
卷 8, 期 21, 页码 -出版社
AME PUBL CO
DOI: 10.21037/atm-20-2554a
关键词
Ferroptosis; pancreatic cancer; immunity; gemcitabine resistance; prognosis
资金
- National Natural Science Foundation of China [81802352]
- National Science Foundation for Distinguished Young Scholars of China [81625016]
- Shanghai Sailing Program [17YF1402500]
- Scientific Innovation Project of Shanghai Education Committee [2019-01-07-00-07-E00057]
- Clinical and Scientific Innovation Project of Shanghai Hospital Development Center [SHDC12018109]
Background: Ferroptosis is a novel form of regulated cell death that can inhibit the progression of chemotherapy-resistant tumors. However, the types of cancer most susceptible to ferroptosis induction and the role of ferroptosis regulators in cancers, especially pancreatic cancer, remain unclear. Methods: RNA sequencing data of 31 cancers were collected from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx). A nomogram integrating patients' clinical information and risk scores based on the expression levels of ferroptosis regulators was depicted. Correlations among the activity levels of 29 immunity-associated gene sets, immune scores, infiltrating immune cells and key ferroptosis regulators were assessed. Results: We performed a pan-cancer analysis and identified 14 distinct cancers that may show a robust response to ferroptosis inducers. Interestingly, the Xc-complex, which is the major target of ferroptosis induction, was upregulated in gemcitabine-resistant pancreatic cancer cells (P<0.05). Furthermore, we focused on the role of ferroptosis regulators in mediating the survival of patients with pancreatic cancer and constructed a prognostic model with good accuracy (AUC =0.713). We also correlated elevated sensitivity to ferroptosis with higher scores for CD8+ T cells (P<0.001), the type two interferon response (P<0.001) and immune checkpoints (P<0.05). Conclusions: We hypothesized that the ferroptosis pathway plays an important role in the prognosis of pancreatic cancer. Immunoand chemotherapy combined with a ferroptosis inducer is a feasible therapeutic approach for pancreatic cancer.
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