title: Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray.
abstract: BACKGROUND
  The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.
  
  
  METHODS
  Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray.
  
  
  RESULTS
  From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.
  
  
  CONCLUSIONS
  Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.
  
  
  CONCLUSIONS
  The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies.
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, Japan. jmatsuba@kuhp.kyoto-u.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Masaya
authors.initials: M
authors.lastname: Ono
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Michimoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Giman
authors.initials: G
authors.lastname: Jung
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakuma
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sata
authors.forename: Hideo
authors.initials: H
authors.lastname: Nagai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimahara
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D000070780:Perilipin-2; D011379:Prognosis; D011446:Prospective Studies; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D020543:Proteome