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Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry
Department of Molecular Biology for Public Health, Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhong Shan Xi Road, Shanghai, 200336, China
Department of Epidemiology, Shanghai Cancer Institute, 2200/25 Xie Tu Road, Shanghai, 200032, China
Department of Epidemiology, School of Public Health; Key Laboratory of Public Health Safety, Ministry of Education, Fudan University,138 Yi Xue Yuan Road, Shanghai, 200032, China
Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA
Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, Bethesda, MD 20892-7234, USA
* Author to whom correspondence should be addressed.
Received: 21 June 2010; in revised form: 5 August 2010 / Accepted: 16 August 2010 / Published: 18 August 2010
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.
Keywords: biliary tract cancers (BTCs); surface-enhanced laser desorption/ionization mass spectrometry (SELDI-TOF-MS); tumor biomarker; protein profiling
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Wang, W.-J.; Xu, W.-H.; Liu, C.-Z.; Rashid, A.; Cheng, J.-R.; Liao, P.; Hu, H.; Chu, L.W.; Gao, Y.-T.; Yu, K.; Hsing, A.W. Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry. Cancers 2010, 2, 1602-1616.
Wang W-J, Xu W-H, Liu C-Z, Rashid A, Cheng J-R, Liao P, Hu H, Chu LW, Gao Y-T, Yu K, Hsing AW. Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry. Cancers. 2010; 2(3):1602-1616.
Wang, Wen-Jing; Xu, Wang-Hong; Liu, Cha-Zhen; Rashid, Asif; Cheng, Jia-Rong; Liao, Ping; Hu, Heng; Chu, Lisa W.; Gao, Yu-Tang; Yu, Kai; Hsing, Ann W. 2010. "Identification of Serum Biomarkers for Biliary Tract Cancers by a Proteomic Approach Based on Time-of-Flight Mass Spectrometry." Cancers 2, no. 3: 1602-1616.