Down-regulation of LXR/RXR activation and negative acute phase response pathways in colon adenocarcinoma revealed by proteomics and bioinformatics analysis

Hui Tang, Saied Mirshahidi, Maheswari Senthil, Kevork Kazanjian, Chien Shing Chen, Kangling Zhang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

BACKGROUND AND OBJECTIVE: Deficiency of vitamin D could be a major cause of colon cancer as suggested as early as 1980 by Drs. Cedric and Frank Garland of the University of California and has recently been underscored by a large European case control study. Whether vitamin D deficiency is because of inadequate intake (food and sunshine) or because of vitamin D metabolism disorder in the patient body is unknown. A proteomics approach to identify protein pathways associated with vitamin D transportation and metabolism pathways will help us understand better the pathology of the colon cancer. METHODS: Lysates of colon adenocarcinoma tissues and their matched healthy tissues, from seven colon cancer patients, have been evaluated by quantitative proteomics and bioinformatics analysis to determine protein expression profiles. Unsupervised hierarchical clustering and principle component analysis (PCA) were utilized for protein expression profiling and biomarker identification, while the reporter ion ratios from tandem-mass-tagging (TMT) labeled peptides were used for quantification. Ingenuity Pathway Analysis (IPA) was used to analyze protein pathways. RESULTS AND CONCLUSION: Proteomics analyses demonstrated that the proteins involved in vitamin D/E binding, heme/iron binding and transportation, and lipid/steroid transportation/metabolic systems were down-regulated in colon cancer and the same set of proteins were down-regulated in the LXR/RXR activation and acute-phase response pathways, revealing a plausible mechanistic connection between vitamin D deficiency, iron homeostasis, and colon cancer.

Original languageEnglish (US)
Pages (from-to)313-324
Number of pages12
JournalCancer Biomarkers
Volume14
Issue number5
DOIs
StatePublished - 2014

Keywords

  • Colorectal cancer
  • LXR/RXR
  • mass spectrometry
  • tandem-masstagging
  • Vitamin D

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics
  • Medicine(all)

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