title: Plasma biomarker discovery and validation for colorectal cancer by quantitative shotgun mass spectrometry and protein microarray.
abstract: The development of a new plasma biomarker for early detection would be necessary to improve the overall outcome of colorectal cancer. Here we report the identification and validation of the ninth component of complement (C9) as a novel plasma biomarker for colorectal cancer by cutting-edge proteomic technologies. Plasma proteins were enzymatically digested into a large array of peptides, and the relative quantity of a total of 94,803 peptide peaks was compared between 31 colorectal cancer patients and 59 age/sex-matched healthy controls using 2D image-converted analysis of liquid chromatography and mass spectrometry. The selected biomarker candidates were validated in 345 subjects (115 colorectal cancer patients and 230 age/sex-matched healthy controls) using high-density reverse-phase protein microarrays. Plasma levels of Apo AI and C9 in colorectal cancer patients significantly differed from healthy controls with P values of 7.94×10(-4) and 1.43×10(-12) (Student's t-test), respectively. In particular, C9 was elevated in patients with colorectal cancer, including those with stage-I and -II diseases (P=3.01×10(-3) and P=1.13×10(-5) , respectively). Although the significance of the present study must be validated in an independent clinical study, the increment of plasma C9 may be applicable to the early detection of colorectal cancer.
authors.affiliation: Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakoshi
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sasazuki
authors.forename: Masaya
authors.initials: M
authors.lastname: Ono
authors.forename: Ayako
authors.initials: A
authors.lastname: Negishi
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakuma
authors.forename: Hideya
authors.initials: H
authors.lastname: Kuwabara
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: Masashi
authors.initials: M
authors.lastname: Shimahara
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Yasunami
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ino
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aoki
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D003186:Complement C9 / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D016632:Apolipoprotein A-I; D014408:Biomarkers, Tumor; D003186:Complement C9