title: Down-regulation of LXR/RXR activation and negative acute phase response pathways in colon adenocarcinoma revealed by proteomics and bioinformatics analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, UTMB at Galveston, TX, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Biospecimen Laboratory, Cancer Center, Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Saied
authors.initials: S
authors.lastname: Mirshahidi
authors.affiliation: Division of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA.
authors.forename: Maheswari
authors.initials: M
authors.lastname: Senthil
authors.affiliation: Division of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA.
authors.forename: Kevork
authors.initials: K
authors.lastname: Kazanjian
authors.affiliation: Cancer Center, Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, UTMB at Galveston, TX, USA.
authors.forename: Kangling
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000210:Acute-Phase Reaction / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006418:Heme / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D047488:Retinoid X Receptors / Q000235:genetics*; D014807:Vitamin D / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047488:Retinoid X Receptors; D014807:Vitamin D; D014810:Vitamin E; D006418:Heme; D007501:Iron
keywords: Colorectal cancer; LXR/RXR; mass spectrometry; tandem-masstagging; vitamin D