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The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

ABSTRACT: Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

SUBMITTER: Wang HC

PROVIDER: S-EPMC10238468 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

Wang Hui-Ching HC Moi Sin-Hua SH Chan Leong-Perng LP Wu Chun-Chieh CC Du Jeng-Shiun JS Liu Pei-Lin PL Chou Meng-Chun MC Wu Che-Wei CW Huang Chih-Jen CJ Hsiao Hui-Hua HH Pan Mei-Ren MR Chen Li-Tzong LT

Experimental & molecular medicine 20230501 5

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the ri ...[more]

PMID: 37121970

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Project description:BackgroundLymphovascular invasion (LOI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), is predictive of poor survival; however, the associated clinical characteristics and underlying molecular mechanisms remain largely unknown.MethodsWe performed weighted gene co-expression network analysis to construct gene co-expression networks and investigate the relationship between key modules and the LOI clinical phenotype. Functional enrichment and KEGG pathway analyses were performed with differentially expressed genes. A protein-protein interaction network was constructed using Cytoscape, and module analysis was performed using MCODE. Prognostic value, expression analysis, and survival analysis were conducted using hub genes; GEPIA and the Human Protein Atlas database were used to determine the mRNA and protein expression levels of hub genes, respectively. Multivariable Cox regression analysis was used to establish a prognostic risk formula and the areas under the receiver operating characteristic curve (AUCs) were used to evaluate prediction efficiency. Finally, potential small molecular agents that could target LOI were identified with DrugBank.ResultsTen co-expression modules in two key modules (turquoise and pink) associated with LOI were identified. Functional enrichment and KEGG pathway analysis revealed that turquoise and pink modules played significant roles in HNSCC progression. Seven hub genes (CNFN, KIF18B, KIF23, PRC1, CCNA2, DEPDC1, and TTK) in the two modules were identified and validated by survival and expression analyses, and the following prognostic risk formula was established: [risk score = EXPDEPDC1 * 0.32636 + EXPCNFN * (- 0.07544)]. The low-risk group showed better overall survival than the high-risk group (P < 0.0001), and the AUCs for 1-, 3-, and 5-year overall survival were 0.582, 0.634, and 0.636, respectively. Eight small molecular agents, namely XL844, AT7519, AT9283, alvocidib, nelarabine, benzamidine, L-glutamine, and zinc, were identified as novel candidates for controlling LOI in HNSCC (P < 0.05).ConclusionsThe two-mRNA signature (CNFN and DEPDC1) could serve as an independent biomarker to predict LOI risk and provide new insights into the mechanisms underlying LOI in HNSCC. In addition, the small molecular agents appear promising for LOI treatment.

Dataset Information

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

Publications

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

Similar Datasets

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