Nonhomologous end joining repair pathway molecules as predictive biomarkers for patients with oral squamous cell carcinoma

• Published in: Journal of cancer research and therapeutics 2021-07, Vol.17 (4), p.1031-1038
• Main Authors: Joshi, Jigna, Vora, Hemangini, Ghosh, Nandita, Tankshali, Rajen, Jetly, Dhaval, Trivedi, Trupti
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cellular signal transduction; Combined Modality Therapy; Development and progression; DNA End-Joining Repair; DNA Ligase ATP - genetics; DNA Ligase ATP - metabolism; DNA Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Follow-Up Studies; Genetic aspects; Humans; Ku Autoantigen - genetics; Ku Autoantigen - metabolism; Male; Middle Aged; Mouth cancer; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Mouth Neoplasms - therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; Oncology, Experimental; Oral cancer; Prognosis; Protein expression; Proteins; Squamous cell carcinoma; Survival analysis; Survival Rate; Young Adult
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/jcrt.JCRT_582_19

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.