Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma

Amino Acids. 2019 May;51(5):813-828. doi: 10.1007/s00726-019-02723-4. Epub 2019 Mar 21.

Abstract

Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.

Keywords: Clinical significance; Esophageal squamous cell carcinoma; Expression pattern; Lysyl oxidase-like 4; Protein–protein interaction network.

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Protein Interaction Maps
  • Protein-Lysine 6-Oxidase
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Amino Acid Oxidoreductases
  • LOXL4 protein, human
  • Protein-Lysine 6-Oxidase