Expression and Prognostic Characteristics of Ferroptosis-Related Genes in Colon Cancer

Zhu, Jie; Zhu, Jie; Xie, Zhengwei

doi:10.3390/ijms22115652

Cited by 20 publications

(15 citation statements)

References 38 publications

(45 reference statements)

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“…In contrast, FANCD2 was found to be a ferroptosis suppressor in bone marrow injury by regulating the expression of iron metabolism and lipid peroxidation-related genes ( 30 ). FANCD2 was identified as a prognostic gene associated with poor prognosis in colon cancer, lung adenocarcinoma, clear cell renal cell carcinoma, and glioma ( 31 – 34 ). PTGS2 , also known as COX-2 , was identified as an upregulated ferroptosis marker during ferroptosis ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma

2023

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Cholangiocarcinoma (CCA) is a highly heterogeneous and aggressive malignancy of the bile ducts with a poor prognosis and high mortality rate. Effective targeted therapy and accurate prognostic biomarkers are still lacking. Ferroptosis is a form of regulated cell death implicated in cancer progression and has emerged as a potential therapeutic target in various cancers. However, a comprehensive analysis of ferroptosis-related genes (FRGs) for predicting CCA prognosis and therapeutic targets and determining the role of ferroptosis in CCA remain to be performed. Here, we developed a prognostic FRG signature using a least absolute shrinkage and selection operator Cox regression analysis in a training cohort. We then validated it using four independent public datasets. The six-FRG signature was developed to predict CCA patient survival, stratifying them into low-risk and high-risk groups based on survival time. Significantly, the high-risk CCA patients had shorter overall survival. A receiver operating characteristic curve analysis further confirmed the prognostic FRG signature’s strong predictive ability, indicating that it was an independent prognostic indicator for CCA patients. Furthermore, the high-risk group was associated with fluke infection and high clinical stages. Cancer-associated fibroblast (CAF) score and CAF markers were significantly higher in the high-risk group than the low-risk group. Moreover, our FRG signature could predict immune checkpoint markers for immunotherapy and drug sensitivity. The mRNA expression levels of the six-FRG signature was validated in 10 CCA cell lines and dividing them into low-risk and high-risk groups using the FRG signature. We further showed that high-risk CCA cell lines were more resistant to ferroptosis inducers, including erastin and RSL3, than the low-risk CCA cell lines. Our study constructed a novel FRG signature model to predict CCA prognoses which might provide prognostic biomarkers and potential therapeutic targets for CCA patients. Ferroptosis sensitivity in high-risk and low-risk CCA cell lines suggests that ferroptosis resistance is associated with high-risk group CCA. Therefore, ferroptosis could be a promising therapeutic target for precision therapy in CCA patients.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma

2023

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“…NOX1 is also included in the ferroptosis gene set. The potential of NOX1 as a ferroptosis-related predictor has been analyzed in many cancers ( Zhu et al, 2021 ; Zhu and Yang, 2021 ). In the rhabdomyosarcoma cell ( Dächert and Ehrenfeld, 2020 ) and non-small lung cancer cell model, NOX1 can affect lipid peroxidation, ROS production, and other aspects to participate in ferroptosis signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Programmed Cell Death Signature in the Prognosis, Tumor Microenvironment and Drug Sensitivity in Lung Adenocarcinoma

et al. 2022

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Programmed cell death (PCD) is a process that regulates the homeostasis of cells in the body, and it plays an important role in tumor immunity. However, the expression profile and clinical characteristics of PCD-related genes remain unclear. In this study, we comprehensively analysed the PCD genes with the tumor microenvironment (TME), drug sensitivity, immunothearapy response, and evaluated their prognostic value through systematic bioinformatics methods.We identified 125 PCD-related regulatory factors, which were expressed differently in lung adenocarcinoma (LUAD) and normal lung tissues. 32 PCD related prognostic genes associated with LUAD were identified by univariate Cox analysis. 23 PCD-related gene signature was constructed, and all LUAD patients in the Cancer Genome Atlas (TCGA) dataset were stratified as low-risk or high-risk groups according to the risk score. This signature had a powerful prognostic value, which was validated in three independent data sets and clinical subtypes. Additionally, it has unique properties in TME. Further analysis showed that different risk groups have different immune cell infiltration, immune inflammation profile, immune pathways, and immune subtypes. In addition, the low-risk group had a better immunotherapy response with higher levels of multiple immune checkpoints and lower Tumor immune dysfunction and exclusion (TIDE) score, while the high-risk group was sensitive to multiple chemotherapeutic drugs because of its lower IC50. In short, this is the first model to predict the prognosis and immunological status of LUAD patients based on PCD-related genes. It may be used as a predictor of immunotherapy response to achieve customized treatment of LUAD.

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“…15 ferroptosis-related genes (FRG) were used for designing a prognosis model recently. It is discovered that highly expressed CISD1, GSS, and FDFT1 are associated with better prognosis, but PEBP1 is related to poor prognosis in stage II colon cancer patients [ 62 ]. In another research, a novel model for colon cancer including 7 FRGs was designed.…”

Section: Ferroptosis and Colon Cancermentioning

confidence: 99%

Non-Canonical Programmed Cell Death in Colon Cancer

Pan

Zheng

Xing

et al. 2022

Cancers

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Programmed cell death (PCD) is an evolutionarily conserved process of cell suicide that is regulated by various genes and the interaction of multiple signal pathways. Non-canonical programmed cell death (PCD) represents different signaling excluding apoptosis. Colon cancer is the third most incident and the fourth most mortal worldwide. Multiple factors such as alcohol, obesity, and genetic and epigenetic alternations contribute to the carcinogenesis of colon cancer. In recent years, emerging evidence has suggested that diverse types of non-canonical programmed cell death are involved in the initiation and development of colon cancer, including mitotic catastrophe, ferroptosis, pyroptosis, necroptosis, parthanatos, oxeiptosis, NETosis, PANoptosis, and entosis. In this review, we summarized the association of different types of non-canonical PCD with tumorigenesis, progression, prevention, treatments, and prognosis of colon cancer. In addition, the prospect of drug-resistant colon cancer therapy related to non-canonical PCD, and the interaction between different types of non-canonical PCD, was systemically reviewed.

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Expression and Prognostic Characteristics of Ferroptosis-Related Genes in Colon Cancer

Cited by 20 publications

References 38 publications

Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma

Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma

Comprehensive Analysis of Programmed Cell Death Signature in the Prognosis, Tumor Microenvironment and Drug Sensitivity in Lung Adenocarcinoma

Non-Canonical Programmed Cell Death in Colon Cancer

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