title: Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry.
abstract: Biliary tract cancers (BTCs) are lethal malignancies currently lacking satisfactory methods for early detection and accurate diagnosis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a promising diagnostic tool for this disease. In this pilot study, sera samples from 50 BTCs and 30 cholelithiasis patients as well as 30 healthy subjects from a population-based case-control study were randomly grouped into training set (30 BTCs, 20 cholelithiasis and 20 controls), duplicate of training set, and blind set (20 BTCs, 10 cholelithiasis and 10 controls); all sets were analyzed on Immobilized Metal Affinity Capture ProteinChips via SELDI-TOF-MS. A decision tree classifier was built using the training set and applied to all test sets. The classification tree constructed with the 3,400, 4,502, 5,680, 7,598, and 11,242 mass-to-charge ratio (m/z) protein peaks had a sensitivity of 96.7% and a specificity of 85.0% when comparing BTCs with non-cancers. When applied to the duplicate set, sensitivity was 66.7% and specificity was 70.0%, while in the blind set, sensitivity was 95.0% and specificity was 75.0%. Positive predictive values of the training, duplicate, and blind sets were 82.9%, 62.5% and 79.2%, respectively. The agreement of the training and duplicate sets was 71.4% (Kappa = 0.43, u = 3.98, P < 0.01). The coefficient of variations based on 10 replicates of one sample for the five differential peaks were 15.8-68.8% for intensity and 0-0.05% for m/z. These pilot results suggest that serum protein profiling by SELDI-TOF-MS may be a promising approach for identifying BTCs but low assay reproducibility may limit its application in clinical practice.
authors.affiliation: Department of Molecular Biology for Public Health, Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhong Shan Xi Road, Shanghai, 200336, China. wanghong.xu@fudan.edu.cn.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wang
authors.forename: Wang-Hong
authors.initials: WH
authors.lastname: Xu
authors.forename: Cha-Zhen
authors.initials: CZ
authors.lastname: Liu
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Cheng
authors.forename: Ping
authors.initials: P
authors.lastname: Liao
authors.forename: Heng
authors.initials: H
authors.lastname: Hu
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing