Abstract

Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan–Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients' overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.

Highlights

  • Head and neck squamous cell carcinomas include several types of malignancies from the oral cavity, pharynx, and larynx

  • Studies have shown the risk factors related to head and neck squamous cell carcinoma (HNSCC) are tobacco use, alcohol consumption, and human papillomavirus (HPV) infection

  • A total of 232 autophagy-related genes (ARGs) were obtained from the Human Autophagy Database (HADb; http://autophagy.lu/clustering/index.html)

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Summary

Introduction

Head and neck squamous cell carcinomas include several types of malignancies from the oral cavity, pharynx, and larynx. Over 600,000 cases are diagnosed worldwide, making HNSCC the sixth most prevalent cancer [1, 2]. Studies have shown the risk factors related to HNSCC are tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. The typical treatments include surgery, radiotherapy, and chemotherapy. The mortality rate of HNSCC remains high, which results in 380,000 death annually mainly because of local recurrence and distant metastasis [3, 4]. It is quite essential to explore an effective and specific signature to help severity assessment and guide decision-making in clinical practice

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