Abstract
In the latest literatures, ferroptosis caused by T cells in cancerous cells provided new insights of improving curative effect of the PD-1/PD-L1 antibody. The microenvironment on which tumor cells develop and survive was also emphasized as its crucial role in tumor occurrence, development, metastasis and immune escape. Thus, the interaction of ferroptosis related genes and tumor microenvironment (TME) was urgently be detected in a comprehensive perspective. We comprehensively evaluated the transcriptional feature of ferroptosis related genes in colon adenocarcinoma (COAD), and systematically associated these ferroptosis subtypes with DNA damage repair (DDR) and TME characteristics. We found two unique patterns of ferroptosis characterized by distinct biological pathways activation. We also demonstrated that FRG score constructed based on ferroptosis subtypes has a significant correlation with prognosis of colon cancer and could act as an independent prognostic biomarker for predicting patients’ survival. The higher immune infiltrating level, immune functional pathways activation was observed in the high FRG score group. Furthermore, these results were verified by an independent external GEO cohort. This work revealed ferroptosis was highly associated with TME complexity and diversity. A novel ferroptosis subtypes related gene scoring system can be used for prognostic prediction in COAD. Targeting ferroptosis may be a therapeutic alternative for COAD.
Highlights
Ferroptosis is a programmed cell death characterized by an iron-dependent oxidative alteration of phospholipid membranes (Conrad et al, 2016)
Higher CNV frequency deletions were found in GOT1, GCLM, FDFT1 CHAC1, SLC7A11, SLC7A11, CRYAB, HSBP1, glutathione peroxidase 4 (GPX4), SLC1A5, FANCD2, and HMGCR, which indicated that CNV could change gene expression in ferroptosis-related genes
According to two recent studies, ferroptosis caused by T cells in cancerous cells provided new insights of improving curative effect of the PD-1/PD-L1 antibody, and only a moderate influence of the PD-L1 antibody has been identified in ferroptosis-insensitive tumor cells (Wang, et al, 2019) (Lang et al, 2019)
Summary
Ferroptosis is a programmed cell death characterized by an iron-dependent oxidative alteration of phospholipid membranes (Conrad et al, 2016). Ferroptosis and Immune Microenvironment phospholipids and suppress arachidonic acid (AA)-metabolizing enzyme activity. This may contribute to the phospholipid peroxidation process (Friedmann Angeli et al, 2014); (Yang et al, 2014); (Ingold et al, 2018); (Kagan et al, 2017). It has become clear that a complex interaction between lipid, iron, and cysteine metabolism is critical for this cell death process. Ferroptosis has been implicated in the development and progression of tumors by activating various regulatory sites in signaling pathways, promoting tumor cell death (Friedmann Angeli et al, 2019) (Tang R. et al, 2020). Elucidating the ferroptosis process and the associated mechanisms that regulate tumor formation may yield novel therapeutic strategies for malignancies (Wu et al, 2020); (Hassannia et al, 2019)
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