Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer

World J Gastroenterol. 2019 Apr 21;25(15):1828-1839. doi: 10.3748/wjg.v25.i15.1828.

Abstract

Background: Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression.

Aim: To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC.

Methods: A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC.

Results: Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases , deeper infiltration depth and later tumor-node-metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC.

Conclusion: LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.

Keywords: Biomarker; Gastric cancer; Hypoxia-inducible factor 1α; Lysyl oxidase; Prognosis.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lymphatic Metastasis / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Protein-Lysine 6-Oxidase / analysis
  • Protein-Lysine 6-Oxidase / metabolism*
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Stomach / pathology
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • LOX protein, human
  • Protein-Lysine 6-Oxidase