Comprehensive characterization of lysosome-dependent cell death reveals prognostic significance and immune landscape in colon adenocarcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Lysosome-dependent cell death (LDCD) genes impact colon adenocarcinoma (COAD) subtypes and patient survival. A five-gene signature predicts prognosis and immunotherapy response, offering new therapeutic targets for colorectal cancer.
Area Of Science
- Oncology
- Molecular Biology
- Immunology
Background
- Lysosome-dependent cell death (LDCD) is a crucial regulated cell death pathway with implications in cancer development and treatment.
- The specific role of LDCD-related genes in colon adenocarcinoma (COAD) is not well-established, necessitating further investigation.
Purpose Of The Study
- To investigate the expression profiles and prognostic significance of LDCD-related genes in COAD.
- To explore the association between LDCD genes, tumor immune microenvironment, and immunotherapy response in COAD.
- To validate the functional role of key LDCD regulators in COAD cell behavior.
Main Methods
- Comprehensive analysis of LDCD-related gene expression using TCGA and GEO transcriptomic data.
- Unsupervised clustering for molecular subtyping, and LASSO/Cox regression for prognostic signature development.
- Assessment of immune infiltration, immunotherapy response, scRNA-seq, and in vitro functional assays (colony formation, Transwell, Western blotting).
Main Results
- LDCD genes were differentially expressed in COAD, defining two molecular subtypes with distinct survival, immune infiltration, and pathway characteristics.
- A five-gene signature accurately predicted overall survival and correlated with tumor immune microenvironment features.
- High-risk patients exhibited specific immune checkpoint profiles and predicted sensitivity to immune checkpoint blockade therapy.
- SLC11A1 was identified as a key regulator affecting COAD cell proliferation, invasion, apoptosis, and ROS levels.
Conclusions
- LDCD-related genes possess significant prognostic value and immunological relevance in COAD.
- The identified molecular subtypes and prognostic signature offer insights for COAD classification and personalized treatment strategies.
- Targeting LDCD pathways, including SLC11A1, presents a potential avenue for novel colorectal cancer therapies.
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