Dataset Information

GDPD5-CD55-EGFR Competitive Binding Axis Regulates Radioresistance and Lipid Accumulation in Rectal Cancer

ABSTRACT: Resistance to neoadjuvant chemoradiotherapy in rectal cancer diminishes survival benefits, potentially due to dysregulated lipid metabolism, though the mechanisms are unclear. 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. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE319208 | GEO | 2026/05/27

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.

Dataset Information

GDPD5-CD55-EGFR Competitive Binding Axis Regulates Radioresistance and Lipid Accumulation in Rectal Cancer

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets