Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Cancer Med. 2020 Nov;9(22):8624-8638. doi: 10.1002/cam4.3472. Epub 2020 Sep 24.

Abstract

Backgrounds: Kidney renal clear cell carcinoma (KIRC) is a major pathological type of renal cell carcinoma (RCC), and the prognosis of advanced KIRC patients is often unsatisfactory. Some lysine oxidase (LOX) family genes have been proven to be upregulated in some malignancies and play pivotal roles in the carcinogenesis. However, their roles in KIRC remain unclear.

Materials and methods: Here, we used some online databases (eg, ONCOMINE, GEPIA, UALCAN, c-BioPortal, Human Protein Altas) to comprehensively explored the expression levels and the prognostic values of LOX family genes in KIRC using bioinformatic methods.

Results: The results revealed that lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2) were significantly overexpressed in KIRC at the level of mRNA expression, protein expression, and RCC cell lines. Further analysis demonstrated that higher mRNA expression of LOX and LOXL2 were significantly correlated with poor survival, tumor grade, individual cancer stages, and nodal metastasis status. DNA copy number amplifications and mRNA upregulation, DNA deep deletion, and mRNA upregulation were the main genetic mutations of LOX and LOXL2, respectively. Prognostic analysis showed that the altered group had significantly poorer overall survival (OS) compared to the unaltered group (p = .0387). Co-expression analysis showed CP, PLOD2, and COL5A1 were significantly correlated with LOX, and COL1A2 was positively correlated with LOXL2. Further analysis confirmed that these co-expressed genes were significantly upregulated and predicted unfavorable prognosis in KIRC.

Conclusion: Multi-level analysis demonstrated that LOX and LOXL2 were significantly upregulated and predicted poor survival in KIRC, which may apply as promising biomarkers for diagnosis and therapy of KIRC in the future.

Keywords: LOX; LOX family genes; LOXL2; extracellular matrix; kidney renal clear cell carcinoma.

Publication types

  • Meta-Analysis

MeSH terms

  • Amino Acid Oxidoreductases / genetics*
  • Amino Acid Oxidoreductases / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Databases, Nucleic Acid
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • Mutation
  • Prognosis
  • Protein Interaction Maps
  • Signal Transduction
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Mixed Function Oxygenases
  • lysine monooxygenase
  • Amino Acid Oxidoreductases
  • LOXL2 protein, human