The underlying molecular mechanism and identification of transcription factor markers for laryngeal squamous cell carcinoma

Bioengineered. 2021 Dec;12(1):208-224. doi: 10.1080/21655979.2020.1862527.

Abstract

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein-protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs - BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 - were screened via Kaplan-Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13-0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.

Keywords: Laryngeal squamous cell carcinoma; RNA sequencing; homeobox B13; prognosis; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Databases, Genetic
  • Female
  • Head and Neck Neoplasms* / diagnosis
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / mortality
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Prognosis
  • Protein Interaction Maps / genetics
  • Squamous Cell Carcinoma of Head and Neck* / diagnosis
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Biomarkers, Tumor
  • HOXB13 protein, human
  • Homeodomain Proteins
  • Transcription Factors

Grants and funding

The study was supported by the funds of National Nature Science Foundation of China [81460479], Guangxi Higher Education Undergraduate Teaching Reform Project [2020JGA146] and Guangxi Medical University Education and Teaching Reform Project [2019XJGZ04].