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Updated: Oct 20, 2025
Author Spotlight: Decoding DNA Repair by Extrachromosomal NHEJ Assay and HR Assays
Published on: February 2, 2024
Nonhomologous end joining repair pathway molecules as predictive biomarkers for patients with oral squamous cell
Jigna S Joshi1, Hemangini H Vora2, Nandita R Ghosh3
1Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.
Purpose:
Nonhomologous end-joining (NHEJ) is critical for the repair of either pathologic double-strand breaks (DSBs) and/or for the repair of physiologic DSBs created during radiotherapy to kill the tumor cell. Therefore, patients with higher expression of NHEJ repair proteins might develop resistance to ionizing radiation, allowing the disease to recur. As cancer of the oral cavity is a serious health problem globally, the present study aimed to examine the expression of Ku70/80, X-ray repair cross-complementing protein 4 (XRCC4) and DNA ligase IV-core molecules of the NHEJ pathway in patients with oral cancer.
Materials And Methods:
Protein expression of Ku70/80, XRCC4, and DNA ligase IV were studied by Immunohistochemistry and mRNA expression of Ku70 and Ku80 were studied using reverse transcription polymerase chain reaction. Data were analyzed statistically using SPSS.
Results:
A univariate survival analysis revealed an association of Ku70 mRNA with shorter overall survival (OS). While protein expression of XRCC4 showed an association with reduced relapse-free survival and shorter OS. Multivariate survival analysis demonstrated that XRCC4 and DNA ligase IV are independent prognosticators for predicting adverse disease outcomes.
Conclusion:
Strong expression of repair proteins - XRCC4 and DNA ligase IV is associated with unfavorable disease outcome in patients with oral squamous cell carcinoma.
Insights
High expression of DNA repair proteins, XRCC4 and DNA ligase IV, in oral cancer patients correlates with poorer survival outcomes and increased relapse risk, indicating their prognostic value.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Nonhomologous end-joining (NHEJ) is a crucial DNA repair pathway for double-strand breaks (DSBs).
- NHEJ proteins may influence resistance to radiotherapy, potentially leading to cancer recurrence.
- Oral cancer is a significant global health concern.
Purpose of the Study:
- To investigate the expression of key NHEJ proteins (Ku70/80, XRCC4, DNA ligase IV) in oral cancer.
- To determine the association between NHEJ protein expression and patient outcomes.
Main Methods:
- Immunohistochemistry was used to assess protein expression of Ku70/80, XRCC4, and DNA ligase IV.
- Reverse transcription polymerase chain reaction (RT-PCR) was employed to measure mRNA levels of Ku70 and Ku80.
- Statistical analysis, including univariate and multivariate survival analyses, was performed.
Main Results:
- Ku70 mRNA expression was linked to shorter overall survival (OS).
- XRCC4 protein expression correlated with reduced relapse-free survival and shorter OS.
- Multivariate analysis identified XRCC4 and DNA ligase IV as independent predictors of adverse outcomes.
Conclusions:
- Elevated expression of XRCC4 and DNA ligase IV is associated with unfavorable prognosis in oral squamous cell carcinoma.
- These findings highlight the potential role of NHEJ proteins in oral cancer progression and treatment response.
