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Development and validation of a hypoxia-related gene pair signature to predict overall survival in head and neck squamous cell carcinoma

  • Head and Neck
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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Objective

Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.

Methods

Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.

Results

A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, T cells CD8, etc. were significantly higher in the low-risk group.

Conclusion

In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

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Availability of data and materials

The raw data of this study are derived from the TCGA database (https://portal.gdc.cancer.gov/) and GEO data portal (https://www.ncbi.nlm.nih.gov/geo/), which are publicly available databases.

Abbreviations

HNSCC:

Head and neck squamous cell carcinoma

HRGPs:

Hypoxia-related gene pairs

OS:

Overall survival

TCGA:

The Cancer Genome Atlas

GEO:

Gene Expression Omnibus

LASSO:

Least absolute shrinkage and selection operator

GO:

Gene Ontology

ROC:

Receiver Operating Characteristic

AUC:

Area Under the ROC Curve

GSEA:

Gene Set Enrichment Analysis

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Authors and Affiliations

  1. Clinical Medical College, Dali University, Dali, 671000, Yunnan, China

    Zhao Ding & Hefeng Li

  2. Department of Otolaryngology, The First Affiliated Hospital of Dali University, Dali, 671000, Yunnan, China

    Deshun Yu

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  1. Zhao Ding
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  2. Hefeng Li
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Contributions

This research was conducted in collaboration with all authors. DZ and LHF performed the data curation and analysis. D.Z. analyzed and interpreted the results. DZ and YDS drafted and reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Deshun Yu.

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Ding, Z., Li, H. & Yu, D. Development and validation of a hypoxia-related gene pair signature to predict overall survival in head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 278, 3973–3983 (2021). https://doi.org/10.1007/s00405-020-06580-w

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