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Ferroptosis and cancer prognosis
Research Guide
What is Ferroptosis and cancer prognosis?
Ferroptosis and cancer prognosis refers to the study of iron-dependent, lipid peroxidation-driven regulated cell death as a factor influencing patient survival outcomes and tumor progression in various cancers.
Research on ferroptosis and cancer prognosis encompasses 54,890 works focused on mechanisms like lipid peroxidation and GPX4 inhibition in tumor cells. Papers examine ferroptosis interactions with the tumor microenvironment, including immune cell infiltration estimated via RNA-sequencing gene expression data. Tools such as UALCAN and TIMER2.0 enable survival analyses linking ferroptosis-related gene expression to prognosis across tumor subgroups.
Topic Hierarchy
Research Sub-Topics
GPX4 Regulation in Ferroptosis
This sub-topic examines GPX4 enzymatic activity, inhibitors like RSL3, and post-translational modifications controlling ferroptosis susceptibility. Researchers identify novel regulators via CRISPR screens.
Lipid Peroxidation Mechanisms in Ferroptosis
This sub-topic investigates PUFA oxidation, lipoxygenase involvement, and lipid droplet dynamics driving ferroptotic execution. Researchers use lipidomics to map peroxidation signatures.
Ferroptosis in Tumor Microenvironment
This sub-topic explores how ferroptosis influences stromal cells, extracellular matrix remodeling, and nutrient competition in TME. Researchers analyze spatial ferroptosis heterogeneity via scRNA-seq.
Immune Cell Ferroptosis in Cancer
This sub-topic studies ferroptosis regulation in T cells, macrophages, and MDSCs within tumors, affecting anti-tumor immunity. Researchers investigate ferroptosis blockade to enhance immunotherapy.
Ferroptosis-Based Cancer Prognosis Signatures
This sub-topic develops gene expression signatures prognostic of ferroptosis vulnerability across cancer types using TCGA data. Researchers validate signatures predicting therapy response.
Why It Matters
Ferroptosis influences cancer prognosis by modulating tumor cell death sensitivity and immune responses in the microenvironment. Yang et al. (2014) in "Regulation of Ferroptotic Cancer Cell Death by GPX4" showed GPX4 inhibition induces ferroptosis in cancer cells, linking this pathway to survival outcomes. Yoshihara et al. (2013) in "Inferring tumour purity and stromal and immune cell admixture from expression data" provided methods to deconvolute immune cell presence, which Thórsson et al. (2018) in "The Immune Landscape of Cancer" correlated with prognosis across 33 cancer types. TIMER2.0 by Li et al. (2020) analyzes tumor-infiltrating immune cells, revealing ferroptosis regulators' prognostic roles, as in UALCAN by Chandrashekar et al. (2017) for subgroup survival analyses.
Reading Guide
Where to Start
"Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death" by Dixon et al. (2012) first, as it provides the foundational definition and mechanisms of ferroptosis essential for understanding its cancer relevance.
Key Papers Explained
Dixon et al. (2012) in "Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death" establishes ferroptosis basics, extended by Yang et al. (2014) in "Regulation of Ferroptotic Cancer Cell Death by GPX4" to cancer-specific GPX4 roles. Stockwell et al. (2017) in "Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease" and Jiang et al. (2021) in "Ferroptosis: mechanisms, biology and role in disease" integrate disease contexts. Yoshihara et al. (2013) in "Inferring tumour purity and stromal and immune cell admixture from expression data" and Chandrashekar et al. (2017) in "UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses" add prognostic tools linking to tumor microenvironments.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Recent analyses leverage TIMER2.0 (Li et al., 2020) for immune cell-ferroptosis interactions and UALCAN for survival in subgroups, building on Thórsson et al. (2018) immune landscapes. No preprints or news in the last 12 months indicate steady progress via expression-based prognosis models.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death | 2012 | Cell | 16.8K | ✓ |
| 2 | Inferring tumour purity and stromal and immune cell admixture ... | 2013 | Nature Communications | 10.3K | ✓ |
| 3 | Regulation of Ferroptotic Cancer Cell Death by GPX4 | 2014 | Cell | 7.0K | ✓ |
| 4 | Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, ... | 2017 | Cell | 6.9K | ✓ |
| 5 | Ferroptosis: mechanisms, biology and role in disease | 2021 | Nature Reviews Molecul... | 6.5K | ✓ |
| 6 | UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expressi... | 2017 | Neoplasia | 6.3K | ✓ |
| 7 | The Immune Landscape of Cancer | 2018 | Immunity | 5.9K | ✓ |
| 8 | TIMER2.0 for analysis of tumor-infiltrating immune cells | 2020 | Nucleic Acids Research | 5.4K | ✓ |
| 9 | Signatures of T cell dysfunction and exclusion predict cancer ... | 2018 | Nature Medicine | 5.3K | ✓ |
| 10 | The consensus molecular subtypes of colorectal cancer | 2015 | Nature Medicine | 5.0K | ✓ |
Frequently Asked Questions
What is ferroptosis in the context of cancer?
Ferroptosis is an iron-dependent form of nonapoptotic cell death driven by lipid peroxidation, as defined in "Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death" by Dixon et al. (2012). In cancer, it targets tumor cells sensitive to GPX4 inhibition. This process links to prognosis via gene expression signatures in tumors.
How does GPX4 regulate ferroptosis in cancer cells?
GPX4 prevents ferroptotic death by reducing lipid hydroperoxides, as shown in "Regulation of Ferroptotic Cancer Cell Death by GPX4" by Yang et al. (2014). Inhibiting GPX4 triggers ferroptosis selectively in cancer cells. This regulation impacts prognosis through altered cell death thresholds in tumors.
What tools analyze ferroptosis-related gene expression for cancer prognosis?
UALCAN facilitates tumor subgroup gene expression and survival analyses, per Chandrashekar et al. (2017) in "UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses". TIMER2.0 infers tumor-infiltrating immune cells from expression data, as in Li et al. (2020). These tools link ferroptosis genes to patient outcomes.
How does the tumor microenvironment affect ferroptosis and prognosis?
Stromal and immune cells in the tumor microenvironment influence ferroptosis via lipid peroxidation and oxidative stress, deconvoluted by Yoshihara et al. (2013) in "Inferring tumour purity and stromal and immune cell admixture from expression data". Thórsson et al. (2018) in "The Immune Landscape of Cancer" mapped immune profiles across cancers correlating with survival. This interplay shapes prognostic signatures.
What role does RNA-sequencing play in ferroptosis-cancer prognosis studies?
RNA-sequencing enables gene expression analysis for ferroptosis markers and immune admixture, as used in TIMER2.0 by Li et al. (2020). It supports survival predictions via tools like UALCAN (Chandrashekar et al., 2017). These methods quantify GPX4-related pathways' prognostic value.
Open Research Questions
- ? How do specific immune cell subsets in the tumor microenvironment modulate ferroptosis resistance and patient survival across cancer types?
- ? What gene expression signatures of GPX4 and lipid peroxidation pathways best predict ferroptosis-driven prognosis in lung and colorectal cancers?
- ? Can deconvolution methods like those in Yoshihara et al. (2013) accurately distinguish ferroptosis effects from stromal interference in bulk tumor RNA-sequencing?
- ? Which molecular subtypes of colorectal cancer, as defined by Guinney et al. (2015), exhibit differential ferroptosis sensitivity linked to immunotherapy response?
- ? How do T cell dysfunction signatures from Jiang et al. (2018) interact with ferroptosis regulators to influence cancer prognosis?
Recent Trends
The field spans 54,890 papers with sustained focus on GPX4 and lipid peroxidation in cancer prognosis, as reviewed in Jiang et al. "Ferroptosis: mechanisms, biology and role in disease". TIMER2.0 (Li et al., 2020) advanced immune cell inference from RNA-sequencing, enhancing microenvironment studies post-Yoshihara et al. (2013).
2021No recent preprints or news signal ongoing reliance on tools like UALCAN for survival analyses.
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