Overexpression of XRCC1 is Associated with Poor Survival in Patients with Head and Neck Squamous Carcinoma and Has Potential to Be Used as Targeted Therapy by Synthetic Lethality

Ahirwar, Sonu Singh; Lasunte, Supriya; Gupta, Manish; Chowdhary, Rashmi; Kotnis, Ashwin

doi:10.31557/APJCP.2023.24.10.3525

Overexpression of XRCC1 is Associated with Poor Survival in Patients with Head and Neck Squamous Carcinoma and Has Potential to Be Used as Targeted Therapy by Synthetic Lethality

Document Type : Research Articles

Authors

¹ Department of Biochemistry, All India Institute of Medical Sciences, Bhopal (M.P.) India.

² Department of Radiotherapy, All India Institute of Medical Sciences, Bhopal (M.P.) India.

10.31557/APJCP.2023.24.10.3525

Abstract

Background: Head neck squamous cell carcinoma (HNSC) is globally prevalent cancer attributed to tobacco habit. Despite the significant advances in early diagnosis and treatment of HNSC chemo-radio resistance are routinely observed in patients. Aberrant DNA repair mechanisms mainly microhomology mediated DNA end joining (MMEJ) pathway causing deleterious mutations and is implicated in treatment resistance. X-ray cross complimenting group 1 (XRCC1) has recently been shown to play an essential role in MMEJ making XRCC1 a potential therapeutic target to render tumors chemo-radiosensitive. This study analyzes the correlation between the expression level of XRCC1 gene with survival, regulation by miRNA and synthetic lethality partners in HNSCC. Materials and Methods: XRCC1 gene expression was evaluated in 520 HNSC patients and 44 of normal tissues using the UALCAN (TCGA) database and its correlation with survival outcome of HNSC patients was analyzed by Kaplan-Meier plot. Infiltration of immune cells in tumors was analyzed by “Tumor-Infiltrating Immune Estimation Resource (TIMER) and promoter methylation status of XRCC1 in samples was analysed by UALCAN. STRING was used to find gene interacting partners of XRCC1. Results: XRCC1 was significantly overexpressed in primary tumor of HNSCC and significantly increased with tumor stages and grade and associated with poor survival rate. High XRCC1 expression in HNSC was positively correlated with infiltration level of B cells naïsve, CD4+ and macrophages. Conclusion: These results indicate that XRCC1 is a prognostic marker for predicting survival in HNSC patients. Understanding how XRCC1 leads to treatment resistance and modulate immune response can lead to development of targeted therapy.

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