Conclusion
Increased TMB and NFE2L2 pathway alterations were associated with radiation resistance in LSCC. NQO1 mRNA expression may serve as a biomarker for RT response in ES-LSCC.Level of Evidence: II1.
Methods
Tumors were classified as either radiation-resistant (RR) or radiation-sensitive (RS). RR was defined as persistent or recurrent disease within 2 years of receiving full-dose RT. Early stage (ES) LSCC was defined as Stage I or II tumors without lymph node involvement. Eight genes associated with radiation resistance were prioritized for analysis. RT-qPCR was performed on five NFE2L2 pathway genes.
Results
Twenty LSCC tumors were included and classified as either RR (n = 8) or RS (n = 12). No differences in individual rates of somatic mutations by genes associated with radiation resistance were identified. Higher rates of total mutational burden (TMB) and increased alterations associated with the NFE2L2 pathway was observed in RR vs RS tumors (P < .05). In an analysis of only ES-LSCC patients (RR, n = 3 and RS, n = 3), RR tumors had increased NFE2L2 somatic pathway mutations (P = .014) and increased NQO1 mRNA expression (P = .05).