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Transcriptomic Profiling Identifies a DNA Repair-Related Signature as a Novel Prognostic Marker in Lower Grade
Fan Zeng1, Xiu Liu2, Kuanyu Wang2
1Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. zengfanjoyce@sina.com.
Background:
Gliomas are the most common and malignant intracranial tumors. The standard therapy is surgical resection combined with radiotherapy and chemotherapy. However, the emergence of radioresistance and chemoresistance, which is largely due to DNA damage repair, limits the therapeutic efficacy. Therefore, we identified a high-efficiency DNA damage repair-related risk signature as a predictor for prognosis in lower grade glioma.
Methods:
The signature was developed and validated in two independent datasets of the Chinese Glioma Genome Atlas (172 samples) and The Cancer Genome Atlas (451 samples). The time-dependent ROC curve, Cox regression, Nomogram, and Kaplan-Meier analyses were performed to evaluate the prognostic performance of the risk signature. The Metascape and IHC staining were performed to reveal the potential biological mechanism. GraphPad prism, SPSS, and R language were used for statistical analysis and graphical work.
Results:
This signature could distinguish the prognosis of patients, and patients with high-risk scores exhibited short survival time. The time-dependent ROC curve, Cox regression, and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with the IDH mutation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell cycle and DNA repair. These mechanisms were confirmed in patient samples.
Conclusions:
The DNA damage repair-related signature was an independent and powerful prognostic biomarker in lower grade glioma.
Impact:
The signature may potentially improve risk stratification of patients and provide a more accurate assessment of personalized treatment in clinic.
Insights
A new DNA damage repair signature predicts prognosis in lower grade glioma. This tool can improve patient risk stratification and personalized treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Gliomas are aggressive brain tumors with limited treatment efficacy due to resistance.
- DNA damage repair mechanisms contribute significantly to therapeutic resistance in gliomas.
- Accurate prognostic biomarkers are crucial for managing lower grade glioma.
Purpose of the Study:
- To identify and validate a DNA damage repair-related risk signature for predicting glioma prognosis.
- To assess the signature's performance as an independent prognostic biomarker.
- To explore the underlying biological mechanisms associated with the signature.
Main Methods:
- Developed and validated a risk signature using two independent glioma datasets (CGGA and TCGA).
- Employed time-dependent ROC, Cox regression, and Nomogram analyses for prognostic evaluation.
- Utilized Metascape and IHC staining to investigate biological mechanisms; statistical analysis performed using R, SPSS, and GraphPad Prism.
Main Results:
- The DNA damage repair signature effectively distinguished patient prognosis, with high-risk scores correlating to shorter survival.
- The signature demonstrated independent prognostic performance and high accuracy for survival prediction.
- Integration with IDH mutation status further refined patient risk stratification; cell cycle and DNA repair pathways were identified as key mechanisms.
Conclusions:
- The developed DNA damage repair-related signature serves as a powerful and independent prognostic biomarker for lower grade glioma.
- This signature has the potential to enhance clinical risk stratification and personalize patient treatment strategies.
- Further validation may lead to improved therapeutic decision-making for glioma patients.
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