English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Objectives  Patients with laryngeal squamous cell carcinoma (LSCC) often fail radiation therapy (RT), when received as monotherapy or in combination with other treatment modalities. Mechanisms for RT failure are poorly understood. We hypothesized that tumors failing RT would have increased rates of somatic mutations in genes associated with radiation resistance, particularly in genes associated with the  NFE2L2  oxidative stress pathway. Using targeted exome sequencing on pretreated LSCC tumors, we retrospectively compared somatic mutation profile with clinical data and response to treatment.    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).    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.

Correlation of alterations in the KEAP1 / CUL3 / NFE2L2 pathway with radiation failure in larynx squamous cell carcinoma