iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance
Open accessAbstract
BACKGROUND: The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance. METHODS: Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects. RESULTS: Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects. CONCLUSIONS: The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Awareness is increasing that obstructive jaundice can lead to false-positive biomarker findings.
“Moreover, awareness that the presence of obstructive jaundice can lead to false-positive biomarker findings is increasing.69–71”
From Early detection of pancreatic cancer (2020) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679 · see citing works
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202 · see citing works
Ross, P. L., Huang, Y. N., Marchese, J. N., Williamson, B., Parker, K., Hattan, S., Khainovski, N., Pillai, S., Dey, S., Daniels, S., et al. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400129-mcp200 · Cited by 4,401 · see citing works
Hidalgo, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0901557 · Cited by 2,570 · see citing works
ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer
Locker, G. Y., Hamilton, S. R., Harris, J. E., Jessup, J. M., Kemeny, N. E., Macdonald, J. S., Somerfield, M. R., Hayes, D. F., & Bast, R. C. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.2644 · Cited by 1,592 · see citing works
Advanced pancreatic carcinoma: current treatment and future challenges
Stathis, A., & Moore, M. J. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.236 · Cited by 791 · see citing works
Sener, S. F., Fremgen, A. M., Menck, H. R., et al. (1999) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(99)00075-7 · Cited by 790 · see citing works
Rosty, C., Christa, L., Kuzdzal, S. A., Baldwin, W. M., ZAHURAK, M. L., Carnot, F., Chan, D. W., Canto, M. I., Lillemoe, K. D., Cameron, J. L., et al. (2002) · PubMed · Cited by 292 · see citing works
A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development
Faça, V. M., Song, K. S., Wang, H., Zhang, Q., Krasnoselsky, A. L., Newcomb, L. F., Plentz, R. R., Gurumurthy, S., Redston, M. S., Pitteri, S. J., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050123 · Cited by 255 · see citing works
CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions
Marrelli, D., Caruso, S., Pedrazzani, C., Neri, A., Fernandes, E., Marini, M., Pinto, E., & Roviello, F. (2009) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2008.12.031 · Cited by 241 · see citing works
Serum Biomarker Panels for the Detection of Pancreatic Cancer
Brand, R. E., Nolen, B. M., Zeh, H. J., Allen, P. J., Eloubeidi, M. A., Goldberg, M. J., Elton, E., Arnoletti, J. P., Christein, J. D., Vickers, S. M., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0248 · Cited by 240 · see citing works
Inter-α-trypsin Inhibitor, a Covalent Protein-Glycosaminoglycan-Protein Complex
Zhuo, L., Hascall, V., & Kimata, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r300039200 · Cited by 229 · see citing works
Tian, M., Cui, Y., Song, G., et al. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-241 · Cited by 216 · see citing works
Okamoto, H. (1999) · Journal of Hepato-Biliary-Pancreatic Surgery · doi:10.1007/s005340050115 · Cited by 195 · see citing works
New biomarkers and targets in pancreatic cancer and their application to treatment
Costello, E., Greenhalf, W., & Neoptolemos, J. P. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.119 · Cited by 192 · see citing works
Self-citationUnderstanding Metastasis in Pancreatic Cancer: A Call for New Clinical Approaches
Tuveson, D. A., & Neoptolemos, J. P. (2012) · Cell · doi:10.1016/j.cell.2011.12.021 · Cited by 188 · see citing works
Self-citationDuraker, N., Hot, S., Polat, Y., Hobek, A. A., Gençler, N., & Urhan, N. (2007) · Journal of Surgical Oncology · doi:10.1002/jso.20604 · Cited by 156 · see citing works
Zhao, J., Patwa, T. H., Qiu, W., Shedden, K., Hinderer, R., Misek, D. E., Anderson, M. A., Simeone, D. M., & Lubman, D. M. (2007) · Journal of Proteome Research · doi:10.1021/pr070062p · Cited by 148 · see citing works
Bauer, A. S., Keller, A., Costello, E., Greenhalf, W., Bier, M., Borries, A., Beier, M., Neoptolemos, J. P., Büchler, M. W., Werner, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034151 · Cited by 118 · see citing works
Self-citationPan, S., Chen, R., Crispin, D. A., May, D., Stevens, T., McIntosh, M. W., Bronner, M. P., Ziogas, A., Anton‐Culver, H., & Brentnall, T. A. (2011) · Journal of Proteome Research · doi:10.1021/pr101148r · Cited by 118 · see citing works
Pancreatic Cancer Serum Detection Using a Lectin/Glyco-Antibody Array Method
Li, C., Simeone, D. M., Brenner, D. E., et al. (2008) · Journal of Proteome Research · doi:10.1021/pr8007013 · Cited by 113 · see citing works
Makawita, S., Smith, C. R., Batruch, I., Zheng, Y., Rückert, F., Grützmann, R., Pilarsky, C. P., Gallinger, S., & Diamandis, E. P. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.008599 · Cited by 113 · see citing works
Singh, S., Tang, S., Sreenarasimhaiah, J., Lara, L. F., & Siddiqui, A. A. (2011) · Digestive Diseases and Sciences · doi:10.1007/s10620-011-1709-8 · Cited by 106 · see citing works
Wong, D., Ko, A. H., Hwang, J. J., Venook, A. P., Bergsland, E. K., & Tempero, M. A. (2008) · Pancreas · doi:10.1097/mpa.0b013e31816d8185 · Cited by 89 · see citing works
Laethem, J. V., Verslype, C., Iovanna, J., Michl, P., Conroy, T., Louvet, C., Hammel, P. R., Mitry, E., Ducreux, M. P., Maraculla, T., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr351 · Cited by 82 · see citing works
Self-citationITIH3 Is a Potential Biomarker for Early Detection of Gastric Cancer
Chong, P. K., Lee, H., Zhou, J., et al. (2010) · Journal of Proteome Research · doi:10.1021/pr100192h · Cited by 81 · see citing works
Smith, R. A., Bosonnet, L., Ghaneh, P., et al. (2008) · Digestive Surgery · doi:10.1159/000140961 · Cited by 79 · see citing works
Yue, T., Maupin, K. A., Fallon, B. P., Li, L., Partyka, K. A., Anderson, M. A., Brenner, D. E., Kaul, K. L., Zeh, H. J., Moser, A. J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029180 · Cited by 76 · see citing works
A technically detailed and pragmatic protocol for quantitative serum proteomics using iTRAQ
Tonack, S., Aspinall-O’Dea, M., Jenkins, R. E., Elliot, V., Murray, S., Lane, C. S., Kitteringham, N. R., Neoptolemos, J. P., & Costello, E. (2009) · Journal of Proteomics · doi:10.1016/j.jprot.2009.07.009 · Cited by 51 · see citing works
Self-citationNew insights for early intervention and detection
Costello, E., & Neoptolemos, J. P. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.214 · Cited by 47 · see citing works
Self-citationAnalysis of Serum Proteins by LC-MS/MS
Tonack, S., Neoptolemos, J. P., & Costello, E. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-780-8_17 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Early detection of pancreatic cancer
Pereira, S. P., Oldfield, L., Ney, A., Hart, P. A., Keane, M. G., Pandol, S. J., Li, D., Greenhalf, W., Jeon, C. Y., Koay, E. J., et al. (2020) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30416-9 · Cited by 482 · see citing works
Self-citationGlycoprotein biomarker panel for pancreatic cancer discovered by quantitative proteomics analysis
Nie, S., Lo, A., Wu, J., Zhu, J., Tan, Z., Simeone, D. M., Anderson, M. A., Shedden, K. A., Ruffin, M. T., & Lubman, D. M. (2014) · Journal of Proteome Research · doi:10.1021/pr400967x · Cited by 128 · see citing works
Jenkinson, C., Elliott, V. L., Evans, A., Oldfield, L., Jenkins, R. E., O'Brien, D. P., Apostolidou, S., Gentry-Maharaj, A., Fourkala, E.-O., Jacobs, I. J., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0879 · Cited by 87 · see citing works
Self-citationBiomarkers for early diagnosis of pancreatic cancer
Jenkinson, C., Earl, J., Ghaneh, P., Halloran, C., Carrato, A., Greenhalf, W., Neoptolemos, J., & Costello, E. (2015) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2015.965145 · Cited by 42 · see citing works
Self-citation
- Authors
- Tonack, S., Jenkinson, C., Cox, T., Elliott, V, Jenkins, R. E., Kitteringham, N. R., Greenhalf, W., Shaw, V, Michalski, C. W., Friess, H., Neoptolemos, J. P., & Costello, E.
- Affiliations
- University of Liverpool (GB)
- TUM Klinikum (DE)
- Corresponding author
- Costello, E
- Venue
- British Journal of Cancer
- Published
- 2013-04-11
- Volume
- 108
- Issue
- 9
- Pages
- 1846-1853
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3658525
- OpenAlex
- W2092846476
- Cited by
- 70
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 5
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Cancer Research UK (16812, A12790, 15957)
- National Institute for Health and Care Research (NF-SI-0510-10126)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic ductal adenocarcinoma, serum biomarkers, obstructive jaundice, biliary obstruction, complement C5, polymeric immunoglobulin receptor, REG3A, CA19-9, pancreatic juice, sensitivity and specificity, combined biomarker detection
- MeSH terms
- Pancreatitis-Associated Proteins, Aged, Alpha-Globulins, Antigens, Neoplasm, Complement C5, Female, Glycoproteins, Humans, Immunoglobulins, Male, Middle Aged, Pancreatic Juice, Pancreatic Neoplasms, Biomarkers, Tumor, CA-19-9 Antigen, Receptors, Polymeric Immunoglobulin, Lectins, C-Type, Jaundice, Obstructive
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
