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Updated: Nov 7, 2025
Author Spotlight: Decoding DNA Repair by Extrachromosomal NHEJ Assay and HR Assays
Published on: February 2, 2024
Comprehensive analysis of DNA damage repair in squamous cell carcinoma subtypes
Fanglu Qin1, Yu Sun2, Kun Deng2
1Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China; Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
Aims:
Defective components resulting from DNA damage and repair mechanisms have been found to be underlying causes that affect the development and progression of different types of cancers, including squamous cell carcinoma (SCC). A more detailed classification of SCC is necessary for better application of DNA damage repair therapies.
Materials And Methods:
We aimed to characterize the molecular profile of SCC by developing a classification system based on DNA damage repair gene expression profiles. An integrative analysis was performed using a metadata set of 1374 SCC human samples from the UCSC Genome Browser. We then analyzed genomic alterations and mutations, and genes-TF-microRNA regulatory relationships and conducted enrichment, survival, and immune infiltration analyses.
Key Findings:
This study was conducted on a total of 1374 SCC patients and 402 DNA damage repair genes. Two subtypes were established using consensus clustering, with 1143 patients being of the Non DDR subtype and 231 patients being of the DDR subtype. MATH, mutation burden, and heterogeneity were significantly higher in Non-DDR subtype than in DDR subtype. Next, a total of 1081 differentially expressed genes and 21 microRNAs were identified between the two subtypes and a genes-TF-microRNA regulatory network was constructed. In addition, stromal score, immune score and ESTIMATE score were significantly lower for the Non-DDR subtype, while tumor purity was significantly lower for the DDR subtype. In addition, five pathways associated with DNA damage repair were all enriched in the DDR subtype.
Significance:
Our study established two subtypes of SCC based on DNA damage repair, which may help to predict prognosis and determine the most suitable treatment for SCC patients.
Insights
Researchers classified squamous cell carcinoma (SCC) into two subtypes based on DNA damage repair (DDR) gene expression. This classification may improve SCC prognosis prediction and treatment selection for patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA damage and repair (DDR) defects are implicated in cancer development, including squamous cell carcinoma (SCC).
- A precise classification of SCC is crucial for tailoring DDR-targeted therapies.
Purpose of the Study:
- To develop a novel classification system for SCC based on DDR gene expression profiles.
- To characterize the molecular distinctions between SCC subtypes.
Main Methods:
- Utilized integrative analysis of 1374 SCC samples from the UCSC Genome Browser.
- Performed consensus clustering based on 402 DDR genes to establish subtypes.
- Analyzed genomic alterations, gene expression, regulatory networks, and immune infiltration.
Main Results:
- Identified two SCC subtypes: DDR (231 patients) and Non-DDR (1143 patients).
- Non-DDR subtype exhibited higher MATH, mutation burden, and heterogeneity.
- DDR subtype showed enrichment in five DDR pathways and distinct immune/stromal scores.
Conclusions:
- Established two SCC subtypes based on DDR profiles, offering potential for improved prognostic prediction.
- This classification may guide personalized treatment strategies for SCC patients.
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