The clinical significance of interleukin 24 and its potential molecular mechanism in laryngeal squamous cell carcinoma

Cancer Biomark. 2020;29(1):111-124. doi: 10.3233/CBM-201441.

Abstract

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86-0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.

Keywords: Interleukin 24; RNA-sequencing; immunohistochemistry; laryngeal squamous cell carcinoma; microarray.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Integrins / genetics
  • Interleukins / genetics*
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 3 / genetics
  • MicroRNAs
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / genetics
  • Protein Interaction Maps / genetics
  • Signal Transduction / genetics
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Transforming Growth Factor beta1 / genetics

Substances

  • Biomarkers, Tumor
  • CSF2 protein, human
  • ITGA5 protein, human
  • Integrins
  • Interleukins
  • MicroRNAs
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • interleukin-24
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1