A Robust Metabolic Enzyme-Based Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Zizhao Mai,Huan Chen,Mingshu Huang,Xinyuan Zhao,Li Cui

doi:10.3389/fonc.2021.770241

Abstract

BackgroundHead and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known.MethodsGene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated.ResultsA total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells.ConclusionOur study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. Moreover, the nomogram model might provide useful guidance for the precision treatment of HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is cancer that arises from squamous cells in the area of the head and neck
The volcano plot was used to visualize the distribution of metabolic enzymes between cancer and normal tissues from the GSE37991 and The Cancer Genome Atlas (TCGA) HNSCC cohort
478 (402 upregulated and 76 downregulated) and 223 (102 upregulated and 121 downregulated) significantly changed metabolic enzymes were identified in GSE37991 and TCGA HNSCC cohort, respectively

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is cancer that arises from squamous cells in the area of the head and neck. HNSCC represents up to 90% of tumors in the head and neck region, which includes malignancy of the oral cavity, pharynx, and larynx [1, 2]. Patients often present with advanced clinical stages at the time of diagnosis that is incurable or requires aggressive treatment, leading to an unfavorable prognosis [5]. This highlights the significance of developing novel and robust molecular signatures for precisely evaluating the clinical outcome of HNSCC, which contributes to therapeutic guidance for HNSCC [6, 7]. Head and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. The underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known

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Discussion

Conclusion