Glycoprotein biomarker panel for pancreatic cancer discovered by quantitative proteomics analysis
Open accessAbstract
Pancreatic cancer is a lethal disease where specific early detection biomarkers would be very valuable to improve outcomes in patients. Many previous studies have compared biosamples from pancreatic cancer patients with healthy controls to find potential biomarkers. However, a range of related disease conditions can influence the performance of these putative biomarkers, including pancreatitis and diabetes. In this study, quantitative proteomics methods were applied to discover potential serum glycoprotein biomarkers that distinguish pancreatic cancer from other pancreas related conditions (diabetes, cyst, chronic pancreatitis, obstructive jaundice) and healthy controls. Aleuria aurantia lectin (AAL) was used to extract fucosylated glycoproteins and then both TMT protein-level labeling and label-free quantitative analysis were performed to analyze glycoprotein differences from 179 serum samples across the six different conditions. A total of 243 and 354 serum proteins were identified and quantified by label-free and TMT protein-level quantitative strategies, respectively. Nineteen and 25 proteins were found to show significant differences in samples between the pancreatic cancer and other conditions using the label-free and TMT strategies, respectively, with 7 proteins considered significant in both methods. Significantly different glycoproteins were further validated by lectin-ELISA and ELISA assays. Four candidates were identified as potential markers with profiles found to be highly complementary with CA 19-9 (p < 0.001). Obstructive jaundice (OJ) was found to have a significant impact on the performance of every marker protein, including CA 19-9. The combination of α-1-antichymotrypsin (AACT), thrombospondin-1 (THBS1), and haptoglobin (HPT) outperformed CA 19-9 in distinguishing pancreatic cancer from normal controls (AUC = 0.95), diabetes (AUC = 0.89), cyst (AUC = 0.82), and chronic pancreatitis (AUC = 0.90). A marker panel of AACT, THBS1, HPT, and CA 19-9 showed a high diagnostic potential in distinguishing pancreatic cancer from other conditions with OJ (AUC = 0.92) or without OJ (AUC = 0.95).
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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 [71]
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Cites
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709 · 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
Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies
Ben, Q., Xu, M., Ning, X., Liu, J., Hong, S., Huang, W., Zhang, H., & Li, Z. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.03.003 · Cited by 685 · see citing works
Depletion of Abundant Plasma Proteins and Limitations of Plasma Proteomics
Tu, C., Rudnick, P. A., Martinez, M. Y., Cheek, K. L., Stein, S. E., Slebos, R. J. C., & Liebler, D. C. (2010) · Journal of Proteome Research · doi:10.1021/pr100646w · Cited by 390 · see citing works
Targeted proteomic strategy for clinical biomarker discovery
Schiess, R., Wollscheid, B., & Aebersold, R. H. (2008) · Molecular Oncology · doi:10.1016/j.molonc.2008.12.001 · Cited by 369 · see citing works
Sweetening the Pot: Adding Glycosylation to the Biomarker Discovery Equation
Drake, P. M., Cho, W., Li, B., Prakobphol, A., Johansen, E., Anderson, N. L., Regnier, F. E., Gibson, B. W., & Fisher, S. J. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2009.136333 · Cited by 302 · see citing works
Mass Spectrometry Based Glycoproteomics—From a Proteomics Perspective
Pan, S., Chen, R., Aebersold, R. H., & Brentnall, T. A. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r110.003251 · Cited by 268 · 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
Self-citationComunale, M. A., Lowman, M., Long, R. E., Krakover, J. D., Philip, R., Seeholzer, S. H., Evans, A. A., HANN, H.-W. L., Block, T. M., & Mehta, A. S. (2006) · Journal of Proteome Research · doi:10.1021/pr050328x · Cited by 221 · see citing works
Early Diagnosis of Pancreatic Cancer: Challenges and New Developments
Kaur, S., Baine, M. J., Jain, M., Sasson, A. R., & Batra, S. K. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.69 · Cited by 221 · see citing works
Evaluation of a Serologic Marker, CA19-9, in the Diagnosis of Pancreatic Cancer
Pleskow, D. K., Berger, H. J., Gyves, J. W., Allen, E., McLean, A. M., & Podolsky, D. K. (1989) · Annals of Internal Medicine · doi:10.7326/0003-4819-110-9-704 · Cited by 180 · see citing works
Sohn, T. A., Lillemoe, K. D., Cameron, J. L., et al. (1999) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(99)00049-6 · Cited by 147 · see citing works
Serum biomarkers for improved diagnostic of pancreatic cancer: a current overview
Bünger, S., Laubert, T., Roblick, U. J., & Habermann, J. K. (2010) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-010-0965-x · Cited by 133 · see citing works
Wu, J., Xie, X., Liu, Y., He, J., Benitez, R. S., Buckanovich, R. J., & Lubman, D. M. (2012) · Journal of Proteome Research · doi:10.1021/pr300330z · Cited by 132 · 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
Chronic inflammation and pancreatic cancer
McKay, C. J., Glen, P., & McMillan, D. C. (2008) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2007.11.007 · Cited by 113 · see citing works
Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer
Wingren, C., Gerdtsson, A. S., Segersvärd, R., Carlsson, A., Andersson, R. E., Löhr, M. J., & Borrebaeck, C. A. K. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2883 · Cited by 111 · see citing works
Using lectins to harvest the plasma/serum glycoproteome
Fanayan, S., Hincapie, M., & Hancock, W. S. (2012) · Electrophoresis · doi:10.1002/elps.201100567 · Cited by 94 · see citing works
Zhu, J., He, J., Liu, Y., et al. (2012) · Journal of Proteome Research · doi:10.1021/pr201059g · Cited by 78 · see citing works
Self-citationLiu, Y., He, J., Li, C., et al. (2009) · Journal of Proteome Research · doi:10.1021/pr900715p · Cited by 77 · see citing works
Mass Spectrometric Assay for Analysis of Haptoglobin Fucosylation in Pancreatic Cancer
Lin, Z., Simeone, D. M., Anderson, M. A., et al. (2011) · Journal of Proteome Research · doi:10.1021/pr200102h · Cited by 77 · see citing works
Self-citationHe, J., Liu, Y., Xie, X., et al. (2010) · Journal of Proteome Research · doi:10.1021/pr100012p · Cited by 73 · see citing works
Zhang, X., Yin, X., Hai-hong, Y., Liu, X., Yang, F., Yao, J., Hong, J., & Yang, P. (2011) · The Analyst · doi:10.1039/c1an15551b · Cited by 72 · see citing works
Tonack, S., Jenkinson, C., Cox, T., Elliott, V, Jenkins, R. E., Kitteringham, N. R., Greenhalf, W., Shaw, V, Michalski, C. W., Friess, H., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.150 · Cited by 70 · see citing works
Matsumoto, H., Shinzaki, S., Narisada, M., et al. (2010) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2010.095 · Cited by 67 · see citing works
Ueda, K., Takami, S., Saichi, N., et al. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.000893 · Cited by 67 · see citing works
Partyka, K. A., Maupin, K. A., Brand, R. E., & Haab, B. B. (2012) · PROTEOMICS · doi:10.1002/pmic.201100676 · Cited by 60 · see citing works
Singh, P. K., Srinivasan, R., & Wig, J. D. (2011) · Pancreas · doi:10.1097/mpa.0b013e31821ff741 · Cited by 56 · see citing works
Diabetes and pancreatic cancer.
Muniraj, T., & Chari, S. T. (2012) · PubMed · Cited by 52 · see citing works
Chu, D., Kohlmann, W., & Adler, D. G. (2016) · PubMed · doi:10.6092/1590-8577/3814 · Cited by 49 · see citing works
Wasan, H. S., Springett, G. M., Chodkiewicz, C., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605243 · Cited by 44 · see citing works
Wehr, A. Y., Hwang, W., Blair, I. A., & Yu, K. H. (2012) · Journal of Proteome Research · doi:10.1021/pr201011f · Cited by 35 · see citing works
Collier, T. S., Randall, S. M., Sarkar, P., Rao, B. M., Dean, R. A., & Muddiman, D. C. (2011) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.5151 · Cited by 34 · see citing works
Abraham, P. E., Giannone, R. J., Adams, R. M., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.022996 · Cited by 34 · see citing works
Nie, S., Lo, A., Zhu, J., et al. (2013) · Analytical Chemistry · doi:10.1021/ac400838s · Cited by 30 · see citing works
Self-citationMolecular and Clinical Markers of Pancreas Cancer
Buxbaum, J. L., & Eloubeidi, M. A. (2015) · PubMed · doi:10.6092/1590-8577/3395 · Cited by 26 · see citing works
Pancreatic Cancer Surveillance: Learning As We Go
Brentnall, T. A. (2011) · The American Journal of Gastroenterology · doi:10.1038/ajg.2011.68 · Cited by 21 · see citing works
The epidemiology of pancreatic cancer
Lakatos, G., & Tulassay, Z. (2010) · Orvosi Hetilap · doi:10.1556/oh.2010.28986 · Cited by 9 · see citing works
Early detection of pancreatic cancer: A possibility in some cases but not a reality in most
Goh, K., & Boon‐Koon, Y. O. O. N. (2012) · Journal of Digestive Diseases · doi:10.1111/j.1751-2980.2012.00609.x · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Sohn T. A.; Lillemoe K. D.; Cameron J. L.; Huang J. J.; Pitt H. A.; Yeo C. J. Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J. Am. Coll. Surg. 1999, 188 6 658– 66 discussion 666–9.. 10359359
Cited by
Sorted by citations
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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
Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers
Kim, J., Bamlet, W. R., Oberg, A. L., Chaffee, K. G., Donahue, G., Cao, X.-J., Chari, S., Garcia, B. A., Petersen, G. M., & Zaret, K. S. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah5583 · Cited by 269 · 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
Xiong, Q., Feng, J., Li, S.-T., Zhang, G.-Y., Qiao, Z.-X., Chen, Z., Wu, Y., Lin, Y., Li, T., Ge, F., et al. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.046003 · Cited by 64 · see citing works
Biomarkers 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
- Authors
- 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.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Lubman, David M.
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-02-26
- Volume
- 13
- Issue
- 4
- Pages
- 1873-1884
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- PMC
- PMC3993962
- OpenAlex
- W2334353005
- Cited by
- 128
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 6 · 2021: 13 · 2020: 7 · 2019: 6 · 2018: 14 · 2017: 19 · 2016: 12 · 2015: 16 · 2014: 8
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Proteome Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (K23DK082097, R01GM49500)
- National Cancer Institute (P50CA130810, R01CA154455)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- pancreatic cancer, biomarker panel, CA19-9, obstructive jaundice, chronic pancreatitis, pancreatic cysts, diabetes mellitus, alpha-1-antichymotrypsin, thrombospondin-1, haptoglobin, fucosylated glycoproteins, Aleuria aurantia lectin, early cancer detection, differential diagnosis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Glycoproteins, Humans, Male, Middle Aged, Pancreatic Neoplasms, ROC Curve, Biomarkers, Tumor, Reproducibility of Results, Proteomics
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