Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study

Lipids Health Dis. 2021 Sep 12;20(1):104. doi: 10.1186/s12944-021-01539-0.

Abstract

Background: Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown.

Methods: Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann-Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC.

Results: The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan-Meier and multivariate regression analyses.

Conclusions: As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.

Keywords: Cholesterol; Colorectal cancer; Ezetimibe; Molecular marker; Niemann-Pick C1-Like 1; Overall survival; Prognosis; Stage.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anticholesteremic Agents / therapeutic use
  • Atlases as Topic
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Cholesterol / blood*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Datasets as Topic
  • Ezetimibe / therapeutic use
  • Female
  • Gene Expression
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Male
  • Membrane Transport Proteins / blood
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Niemann-Pick Disease, Type C / diagnosis
  • Niemann-Pick Disease, Type C / drug therapy
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / mortality
  • Prognosis
  • Proportional Hazards Models
  • Sex Factors
  • Survival Analysis

Substances

  • Anticholesteremic Agents
  • Biomarkers, Tumor
  • Membrane Transport Proteins
  • NPC1L1 protein, human
  • Cholesterol
  • Ezetimibe