Identification of LCN1 as a Potential Biomarker for Breast Cancer by Bioinformatic Analysis

DNA Cell Biol. 2019 Oct;38(10):1088-1099. doi: 10.1089/dna.2019.4843. Epub 2019 Aug 19.

Abstract

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan-Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis.

Keywords: LCN1; breast cancer; genomic mutation; immune enrichment; survival analysis.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • DNA Copy Number Variations
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lipocalin 1 / genetics*
  • Lipocalin 1 / immunology
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Perimenopause / genetics
  • Postmenopause / genetics
  • Postmenopause / immunology
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / immunology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • LCN1 protein, human
  • Lipocalin 1
  • ERBB2 protein, human
  • Receptor, ErbB-2