Abstract

PurposeTo construct a prognostic signature composed of DNA repair genes to effectively predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).MethodsAfter downloading the transcriptome and clinical data of HNSCC from the Cancer Genome Atlas (TCGA), 499 patients with HNSCC were equally divided into training and testing sets. In the training set, 13 DNA repair genes were screened using univariate proportional hazard (Cox) regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a risk model, which was validated in the testing set.ResultsIn the training and testing sets, there were significant differences in the clinical outcomes of patients in the high- and low-risk groups showed by Kaplan-Meier survival curves (P < 0.001). Univariate and multivariate Cox regression analyses showed that the risk score had independent prognostic predictive ability (P < 0.001). At the same time, the immune cell infiltration, immune score, immune-related gene expression, and tumor mutation burden (TMB) of patients with HNSCC were also different between the high- and low-risk groups (P < 0.05). Finally, we screened several chemotherapeutics for HNSCC, which showed significant differences in drug sensitivity between the high- and low-risk groups (P < 0.05).ConclusionThis study constructed a 13-DNA-repair-gene signature for the prognosis of HNSCC, which could accurately and independently predict the clinical outcome of the patient. We then revealed the immune landscape, TMB, and sensitivity to chemotherapy drugs in different risk groups, which might be used to guide clinical treatment decisions.

Highlights

  • Head and neck squamous cell carcinoma (HNSCC) is a type of tumor that originates from the squamous epithelium of the head and neck areas, including the mucous membranes of the lips, tongue, pharynx, larynx, and others [1]

  • The results showed that the risk model composed of DNA repair genes could effectively distinguish patients with different clinical outcomes and has independent predictive prognostic ability

  • The transcriptome profiling (RNA-seq) data harmonized to fragments per kilobase million (FPKM), clinical information, and tumor mutations in patients with HNSCC were downloaded from the Cancer Genome Atlas (TCGA) database in March 2021 [9]

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Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is a type of tumor that originates from the squamous epithelium of the head and neck areas, including the mucous membranes of the lips, tongue, pharynx, larynx, and others [1]. A Prognostic Signature for HNSCC tumors in 2020, respectively [2]. HNSCC is highly malignant, and there are no specific prognostic-related biomarkers for clinical application. Prognostic-related biomarkers with clinical applicability are urgently required. DNA damage and repair play important roles throughout the life of a cell [3]. DNA damage affects the expression of a variety of genes, including proto-oncogenes and cancer suppressor genes. Changes in the activity of proto-oncogenes and cancer suppressor genes are crucial in tumorigenesis [4]. Several DNA repair genes have been confirmed to play an important role in the development and prognosis of HNSCC [5,6,7].

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