![]() Sequencing and quality control data are shown in Supplementary Materials Tables S1–S3. Thus, we performed library preparation, targeted capture with our custom library, and next generation sequencing to an average sequencing depth >3000X for our 62 patient cohort. We also included known actionable genes such as BRAF and PDL1 ( CD274) in the analysis. To test genetic alterations that may be associated with differential prognoses in this cohort, we focused on a list of candidate genes that were altered at >2% frequency in the original Head and Neck TCGA project, which included 226 candidate gene biomarkers, ranging from high frequency alterations such as TP53 and PIK3CA, to low frequency alterations such as HRAS and MDM2. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. ![]() Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1–9.2, p = 0.03). 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Recurrence thereafter is associated with poor survival. Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer.
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