| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Clinical Oncology, the Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, the People’s Republic of China.
2 Ciphergen Biosystems, Inc., Fremont, CA 94555.
3 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, England.
aAddress correspondence to this author at: Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. Fax 852-2649-7426. or Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, England. E-mail JohnsonP{at}cancer.bham.ac.uk.
Background: Detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is difficult. We investigated the use of comprehensive proteomic profiling of sera to differentiate HCC from CLD.
Methods: Proteomes in sera from 20 CLD patients with 
-fetoprotein (AFP) <500 µg/L (control group) and 38 HCC patients (disease group) were profiled by anion-exchange fractionation (first dimension), two types (IMAC3 copper and WCX2) of ProteinChip® Arrays (second dimension), and time-of-flight mass spectrometry (third dimension). Bioinformatic tests were used to identify tumor-specific proteomic features and to estimate the values of the tumor-specific proteomic features in the diagnosis of HCC. Cross-validation was performed, and we also validated the models with pooled sera from the control and disease groups, serum from a CLD patient with AFP >500 µg/L, and postoperative sera from two HCC patients.
Results: Among 2384 common serum proteomic features, 250 were significantly different between the HCC and CLD cases. Two-way hierarchical clustering differentiated HCC and CLD cases. Most HCC cases with advanced disease were clustered together and formed two subgroups that contained significantly more cases with lymph node invasion or distant metastasis. For differentiation of HCC and CLD by an artificial network (ANN), the area under the ROC curve was 0.91 (95% confidence interval, 0.82–1.01; P <0.0005) for all cases and 0.954 (95% confidence interval, 0.881–1.027; P <0.0005) for cases with nondiagnostic serum AFP (<500 µg/L). At a specificity of 90%, the sensitivity was 92%. Both cluster analysis and ANN correctly classified the pooled serum samples, the CLD serum sample with increased AFP, and the HCC patient in complete remission.
Conclusion: Tumor-specific proteomic signatures may be useful for detection and classification of hepatocellular cancers.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  R. W. C. Pang, J. W. Joh, P. J. Johnson, M. Monden, T. M. Pawlik, and R. T. P. Poon Biology of Hepatocellular Carcinoma Ann. Surg. Oncol., April 1, 2008; 15(4): 962 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Zinkin, F. Grall, K. Bhaskar, H. H. Otu, D. Spentzos, B. Kalmowitz, M. Wells, M. Guerrero, J. M. Asara, T. A. Libermann, et al. Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease Clin. Cancer Res., January 15, 2008; 14(2): 470 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bennett Untargeted Metabolomic Analysis Hits the Target Clin. Chem., December 1, 2007; 53(12): 2037 - 2039. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Sun, B. Xing, Y. Sun, X. Du, M. Lu, C. Hao, Z. Lu, W. Mi, S. Wu, H. Wei, et al. Proteome Analysis of Hepatocellular Carcinoma by Two-dimensional Difference Gel Electrophoresis: Novel Protein Markers in Hepatocellular Carcinoma Tissues Mol. Cell. Proteomics, October 1, 2007; 6(10): 1798 - 1808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K.T. Kam, T. C.W. Poon, H. L.Y. Chan, N. Wong, A. Y. Hui, and J. J.Y. Sung High-Throughput Quantitative Profiling of Serum N-Glycome by MALDI-TOF Mass Spectrometry and N-Glycomic Fingerprint of Liver Fibrosis Clin. Chem., July 1, 2007; 53(7): 1254 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Otu, H. Can, D. Spentzos, R. G. Nelson, R. L. Hanson, H. C. Looker, W. C. Knowler, M. Monroy, T. A. Libermann, S. A. Karumanchi, et al. Prediction of Diabetic Nephropathy Using Urine Proteomic Profiling 10 Years Prior to Development of Nephropathy Diabetes Care, March 1, 2007; 30(3): 638 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Aivado, D. Spentzos, U. Germing, G. Alterovitz, X.-Y. Meng, F. Grall, A. A. N. Giagounidis, G. Klement, U. Steidl, H. H. Otu, et al. From the cover: Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease PNAS, January 23, 2007; 104(4): 1307 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T.K. Pang, T. C.W. Poon, K.C. A. Chan, N. L.S. Lee, R. W.K. Chiu, Y.-K. Tong, R. M.Y. Wong, S. S.C. Chim, S. M. Ngai, J. J.Y. Sung, et al. Serum Proteomic Fingerprints of Adult Patients with Severe Acute Respiratory Syndrome Clin. Chem., March 1, 2006; 52(3): 421 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Hortin and B. Meilinger Cross-Reactivity of Amino Acids and Other Compounds in the Biuret Reaction: Interference with Urinary Peptide Measurements Clin. Chem., August 1, 2005; 51(8): 1411 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kim, P. Sun, Y.-W. Lam, P. Troncoso, A. L. Sabichi, R. J. Babaian, L. L. Pisters, C. A. Pettaway, C. G. Wood, S. M. Lippman, et al. Changes in Serum Proteomic Patterns by Presurgical {alpha}-Tocopherol and L-Selenomethionine Supplementation in Prostate Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1697 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Meyerson and D. Carbone Genomic and Proteomic Profiling of Lung Cancers: Lung Cancer Classification in the Age of Targeted Therapy J. Clin. Oncol., May 10, 2005; 23(14): 3219 - 3226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Le, K. Chi, S. Tyldesley, S. Flibotte, D. L. Diamond, M. A. Kuzyk, and M. D. Sadar Identification of Serum Amyloid A as a Biomarker to Distinguish Prostate Cancer Patients with Bone Lesions Clin. Chem., April 1, 2005; 51(4): 695 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Malik, M. D. Ward, S. K. Gupta, M. W. Trosset, W. E. Grizzle, B.-L. Adam, J. I. Diaz, and O. J. Semmes Serum Levels of an Isoform of Apolipoprotein A-II as a Potential Marker for Prostate Cancer Clin. Cancer Res., February 1, 2005; 11(3): 1073 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C.W. Poon, A. Y. Hui, H. L.Y. Chan, I. L. Ang, S. M. Chow, N. Wong, and J. J.Y. Sung Prediction of Liver Fibrosis and Cirrhosis in Chronic Hepatitis B Infection by Serum Proteomic Fingerprinting: A Pilot Study Clin. Chem., February 1, 2005; 51(2): 328 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Semmes, Z. Feng, B.-L. Adam, L. L. Banez, W. L. Bigbee, D. Campos, L. H. Cazares, D. W. Chan, W. E. Grizzle, E. Izbicka, et al. Evaluation of Serum Protein Profiling by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Detection of Prostate Cancer: I. Assessment of Platform Reproducibility Clin. Chem., January 1, 2005; 51(1): 102 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Drake, R. A.R. Bowen, A. T. Remaley, and G. L. Hortin Potential Interferences from Blood Collection Tubes in Mass Spectrometric Analyses of Serum Polypeptides Clin. Chem., December 1, 2004; 50(12): 2398 - 2401. [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Wetmore and B. A. Merrick Invited Review: Toxicoproteomics: Proteomics Applied to Toxicology and Pathology Toxicol Pathol, October 1, 2004; 32(6): 619 - 642. [Abstract] [PDF]
|
|
|
|
|
|
T. C.W. Poon, K.C. A. Chan, P.-C. Ng, R. W.K. Chiu, I. L. Ang, Y.-k. Tong, E. K.O. Ng, F. W.T. Cheng, A. M. Li, E. K.L. Hon, et al. Serial Analysis of Plasma Proteomic Signatures in Pediatric Patients with Severe Acute Respiratory Syndrome and Correlation with Viral Load Clin. Chem., August 1, 2004; 50(8): 1452 - 1455. [Full Text] [PDF]
|
|
|
|
|
|
S. G. Soltys, Q.-T. Le, G. Shi, R. Tibshirani, A. J. Giaccia, and A. C. Koong The Use of Plasma Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Proteomic Patterns for Detection of Head and Neck Squamous Cell Cancers Clin. Cancer Res., July 15, 2004; 10(14): 4806 - 4812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Xiao, B. T. Luke, G. Izmirlian, A. Umar, P. M. Lynch, R. K. S. Phillips, S. Patterson, T. P. Conrads, T. D. Veenstra, P. Greenwald, et al. Serum Proteomic Profiles Suggest Celecoxib-Modulated Targets and Response Predictors Cancer Res., April 15, 2004; 64(8): 2904 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Koopmann, Z. Zhang, N. White, J. Rosenzweig, N. Fedarko, S. Jagannath, M. I. Canto, C. J. Yeo, D. W. Chan, and M. Goggins Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry Clin. Cancer Res., February 1, 2004; 10(3): 860 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ramdani, V. Nuyens, T. Codden, G. Perpete, J. Colicis, A. Lenaerts, J.-P. Henry, and F. J. Legros Analyte Comigrating with Trisialotransferrin during Capillary Zone Electrophoresis of Sera from Patients with Cancer Clin. Chem., November 1, 2003; 49(11): 1854 - 1864. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
