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Published in: Clinical and Experimental Medicine 1/2017

01-02-2017 | Original Article

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Authors: Yun-Peng Zhao, Ping-Ting Zhou, Wei-Ping Ji, Hao Wang, Meng Fang, Meng-Meng Wang, Yue-Peng Yin, Gang Jin, Chun-Fang Gao

Published in: Clinical and Experimental Medicine | Issue 1/2017

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Abstract

Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA–FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.
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Literature
1.
3.
go back to reference Ueno H, Kosuge T, Matsuyama Y, et al. A randomized phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101:908–15.CrossRefPubMedPubMedCentral Ueno H, Kosuge T, Matsuyama Y, et al. A randomized phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101:908–15.CrossRefPubMedPubMedCentral
4.
go back to reference Ni XG, Bai XF, Mao YL, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol. 2005;31:164–9.CrossRefPubMed Ni XG, Bai XF, Mao YL, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol. 2005;31:164–9.CrossRefPubMed
5.
go back to reference Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107:15–22.CrossRefPubMed Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107:15–22.CrossRefPubMed
6.
7.
go back to reference Ravindranath MH, Yesowitch P, Sumobay C, et al. Glycoimmunomics of human cancer: current concepts and future perspectives. Future Oncol. 2007;3:201–14.CrossRefPubMed Ravindranath MH, Yesowitch P, Sumobay C, et al. Glycoimmunomics of human cancer: current concepts and future perspectives. Future Oncol. 2007;3:201–14.CrossRefPubMed
8.
go back to reference Arnold JN, Saldova R, Hamid UM, et al. Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation. Proteomics. 2008;8:3284–93.CrossRefPubMed Arnold JN, Saldova R, Hamid UM, et al. Evaluation of the serum N-linked glycome for the diagnosis of cancer and chronic inflammation. Proteomics. 2008;8:3284–93.CrossRefPubMed
9.
go back to reference Lech G, Slotwinski R, Krasnodebski IW. The role of tumor markers and biomarkers in colorectal cancer. Neoplasma. 2014;61:1–8.CrossRefPubMed Lech G, Slotwinski R, Krasnodebski IW. The role of tumor markers and biomarkers in colorectal cancer. Neoplasma. 2014;61:1–8.CrossRefPubMed
10.
go back to reference Ruhaak LR, Miyamoto S, Lebrilla CB. Developments in the identification of glycan biomarkers for the detection of cancer. Mol Cell Proteomics. 2013;12:846–55.CrossRefPubMedPubMedCentral Ruhaak LR, Miyamoto S, Lebrilla CB. Developments in the identification of glycan biomarkers for the detection of cancer. Mol Cell Proteomics. 2013;12:846–55.CrossRefPubMedPubMedCentral
13.
go back to reference Callewaert N, Van Vlierberghe H, Van Hecke A, et al. Noninvasive diagnosis of liver cirrhosis using DNA sequencer based total serum protein glycomics. Nat Med. 2004;10:429–34.CrossRefPubMed Callewaert N, Van Vlierberghe H, Van Hecke A, et al. Noninvasive diagnosis of liver cirrhosis using DNA sequencer based total serum protein glycomics. Nat Med. 2004;10:429–34.CrossRefPubMed
14.
go back to reference Lebrilla CB, An HJ. The prospects of glycan biomarkers for the diagnosis of diseases. Mol BioSyst. 2009;5:17–20.CrossRefPubMed Lebrilla CB, An HJ. The prospects of glycan biomarkers for the diagnosis of diseases. Mol BioSyst. 2009;5:17–20.CrossRefPubMed
15.
go back to reference Wong D, Ko AH, Hwang J, et al. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37:269–74.CrossRefPubMed Wong D, Ko AH, Hwang J, et al. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37:269–74.CrossRefPubMed
16.
go back to reference Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107:15–22.CrossRefPubMed Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol. 2013;107:15–22.CrossRefPubMed
17.
go back to reference Singh S, Tang SJ, Sreenarasimhaiah J, et al. The clinical utility and limitations of serum carbohydrate antigen (CA19-9) as a diagnostic tool for pancreatic cancer and cholangiocarcinoma. Dig Dis Sci. 2011;56:2491–6.CrossRefPubMed Singh S, Tang SJ, Sreenarasimhaiah J, et al. The clinical utility and limitations of serum carbohydrate antigen (CA19-9) as a diagnostic tool for pancreatic cancer and cholangiocarcinoma. Dig Dis Sci. 2011;56:2491–6.CrossRefPubMed
18.
19.
go back to reference Smith RA, Bosonnet L, Ghaneh P, Neoptolemos JP, et al. Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma. Dig Surg. 2008;25:226–32.CrossRefPubMed Smith RA, Bosonnet L, Ghaneh P, Neoptolemos JP, et al. Preoperative CA19-9 levels and lymph node ratio are independent predictors of survival in patients with resected pancreatic ductal adenocarcinoma. Dig Surg. 2008;25:226–32.CrossRefPubMed
20.
go back to reference Ballehaninna UK, Chamberlain RS. Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19-9. Tumour Biol. 2013;34:3279–92.CrossRefPubMed Ballehaninna UK, Chamberlain RS. Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19-9. Tumour Biol. 2013;34:3279–92.CrossRefPubMed
21.
go back to reference Shaw VE, Lane B, Jenkinson C, Cox T, et al. Serum cytokine biomarker panels for discriminating pancreatic cancer from benign pancreatic disease. Mol Cancer. 2014;13:114.CrossRefPubMedPubMedCentral Shaw VE, Lane B, Jenkinson C, Cox T, et al. Serum cytokine biomarker panels for discriminating pancreatic cancer from benign pancreatic disease. Mol Cancer. 2014;13:114.CrossRefPubMedPubMedCentral
22.
go back to reference Pilobello KT, Mahal LK. Lectin microarrays for glycoprotein analysis. Methods Mol Biol. 2007;385:193–203.CrossRefPubMed Pilobello KT, Mahal LK. Lectin microarrays for glycoprotein analysis. Methods Mol Biol. 2007;385:193–203.CrossRefPubMed
23.
go back to reference Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126:855–67.CrossRefPubMed Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126:855–67.CrossRefPubMed
25.
go back to reference Wang J, Zhou C, Zhang W, et al. An integrative strategy for quantitative analysis of the N-glycoproteome in complex biological samples. Proteome Sci. 2014;12:4.CrossRefPubMedPubMedCentral Wang J, Zhou C, Zhang W, et al. An integrative strategy for quantitative analysis of the N-glycoproteome in complex biological samples. Proteome Sci. 2014;12:4.CrossRefPubMedPubMedCentral
27.
go back to reference Pochechueva T, Jacob F, Fedier A, et al. Tumor-associated glycans and their role in gynecological cancers: accelerating translational research by novel high-throughput approaches. Metabolites. 2012;2:913–39.CrossRefPubMedPubMedCentral Pochechueva T, Jacob F, Fedier A, et al. Tumor-associated glycans and their role in gynecological cancers: accelerating translational research by novel high-throughput approaches. Metabolites. 2012;2:913–39.CrossRefPubMedPubMedCentral
28.
go back to reference Ono M, Hakomori S. Glycosylation defining cancer cell motility and invasiveness. Glycoconj J. 2004;20:71–8.CrossRefPubMed Ono M, Hakomori S. Glycosylation defining cancer cell motility and invasiveness. Glycoconj J. 2004;20:71–8.CrossRefPubMed
29.
go back to reference Fang M, Zhao YP, Zhou FG, et al. N-glycan based models improve diagnostic efficacies in hepatitis B virus-related hepatocellular carcinoma. Int J Cancer. 2010;127:148–59.CrossRefPubMed Fang M, Zhao YP, Zhou FG, et al. N-glycan based models improve diagnostic efficacies in hepatitis B virus-related hepatocellular carcinoma. Int J Cancer. 2010;127:148–59.CrossRefPubMed
30.
go back to reference Zhao YP, Ruan CP, Wang H, et al. Identification and assessment of new biomarkers for colorectal cancer with serum N-glycan profiling. Cancer. 2012;118:639–50.CrossRefPubMed Zhao YP, Ruan CP, Wang H, et al. Identification and assessment of new biomarkers for colorectal cancer with serum N-glycan profiling. Cancer. 2012;118:639–50.CrossRefPubMed
32.
go back to reference Bloomston M, Bekaii-Saab TS, Kosuri K, et al. Preoperative carbohydrate antigen 19-9 is most predictive of malignancy in older jaundiced patients undergoing pancreatic resection. Pancreas. 2006;33:246–9.CrossRefPubMed Bloomston M, Bekaii-Saab TS, Kosuri K, et al. Preoperative carbohydrate antigen 19-9 is most predictive of malignancy in older jaundiced patients undergoing pancreatic resection. Pancreas. 2006;33:246–9.CrossRefPubMed
33.
go back to reference Vestergaard EM, Hein HO, Meyer H, et al. Reference values and biological variation for tumor marker CA19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999;45:54–61.PubMed Vestergaard EM, Hein HO, Meyer H, et al. Reference values and biological variation for tumor marker CA19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999;45:54–61.PubMed
34.
go back to reference Salvini R, Bardoni A, Valli M, et al. Beta 1,3-Galactosyltransferase beta 3Gal-T5 acts on the GlcNAcbeta 1–>3Galbeta 1–>4GlcNAcbeta 1–>R sugar chains of carcinoembryonic antigen and other N-linked glycoproteins and is down-regulated in colon adenocarcinomas. J Biol Chem. 2001;276:3564–73.CrossRefPubMed Salvini R, Bardoni A, Valli M, et al. Beta 1,3-Galactosyltransferase beta 3Gal-T5 acts on the GlcNAcbeta 1–>3Galbeta 1–>4GlcNAcbeta 1–>R sugar chains of carcinoembryonic antigen and other N-linked glycoproteins and is down-regulated in colon adenocarcinomas. J Biol Chem. 2001;276:3564–73.CrossRefPubMed
35.
go back to reference Liao WC, Tu YK, Wu MS, et al. Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis. BMJ. 2015;349:g7371.CrossRefPubMed Liao WC, Tu YK, Wu MS, et al. Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis. BMJ. 2015;349:g7371.CrossRefPubMed
36.
go back to reference Tonack S, Jenkinson C, Cox T, et al. iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance. Br J Cancer. 2013;108:1846–53.CrossRefPubMedPubMedCentral Tonack S, Jenkinson C, Cox T, et al. iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance. Br J Cancer. 2013;108:1846–53.CrossRefPubMedPubMedCentral
Metadata
Title
Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer
Authors
Yun-Peng Zhao
Ping-Ting Zhou
Wei-Ping Ji
Hao Wang
Meng Fang
Meng-Meng Wang
Yue-Peng Yin
Gang Jin
Chun-Fang Gao
Publication date
01-02-2017
Publisher
Springer International Publishing
Published in
Clinical and Experimental Medicine / Issue 1/2017
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-015-0401-2

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