Omics · study · 2026
GDPD5-CD55-EGFR Competitive Binding Axis Regulates Radioresistance and Lipid Accumulation in Rectal Cancer
Listed in NCBI GEO
Resistance to neoadjuvant chemoradiotherapy in rectal cancer diminishes survival benefits, potentially due to dysregulated lipid metabolism, though the mechanisms are unclear.
Description
Using the MSigDB database and GSE68204 cohort, we identified lipid metabolism genes linked to radiotherapy resistance. We developed resistant cell lines and xenograft models, and through multi-algorithm analysis (SVM-RFE, RF, LASSO), pinpointed key genes.
Molecular mechanisms were explored via Western blotting, co-immunoprecipitation, molecular docking, and functional assays, validated in patient-derived organoids. Our study found that radiotherapy-resistant rectal cancer shows a lipid accumulation phenotype, with an inverse relationship between lipid droplet deposition and radiosensitivity in resistant cell models. The multi-algorithm screening identified GDPD5 as a key regulator.
Read the rest (2 more)
Silencing GDPD5 reduced lipid accumulation and increased radiosensitivity. Mechanistically, GDPD5 competes with CD55, disrupting its interaction with EGFR and promoting EGFR nuclear translocation, which suppresses p53 and leads to lipid buildup and radiotherapy resistance in tumors. Clinical samples showed high GDPD5 and low CD55 levels correlate with EGFR nuclear localization.
Patient-derived organoids with high GDPD5 also showed increased radiotherapy resistance. Our findings indicate that GDPD5 facilitates EGFR nuclear translocation by binding to CD55, suppressing p53, and causing lipid accumulation and radiotherapy resistance in tumors. Targeting the GDPD5-CD55-EGFR interaction may enhance radiosensitivity.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319208 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319208 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1422628 ncbi.nlm.nih.gov/bioproject/PRJNA1422628 ↗
project · from NCBI GEO
- PubMed 41946696 pubmed.ncbi.nlm.nih.gov/41946696 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE319208 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |