Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Nicolai A Schultz; Ib Jarle Christensen; Jens Werner; Nathalia Giese; Benny V Jensen; Ole Larsen; Jon K Bjerregaard; Per Pfeiffer; Dan Calatayud; Svend E Nielsen; Mette Karen Yilmaz; Niels H Holländer; Morten Wøjdemann; Stig E Bojesen; Kaspar Rene Nielsen; Julia S Johansen

doi:10.1371/journal.pone.0067059

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Nicolai A Schultz, Ib Jarle Christensen, Jens Werner, Nathalia Giese, Benny V Jensen, Ole Larsen, Jon K Bjerregaard, Per Pfeiffer, Dan Calatayud, Svend E Nielsen, Mette Karen Yilmaz, Niels H Holländer, Morten Wøjdemann, Stig E Bojesen, Kaspar Rene Nielsen, Julia S Johansen

24 Citations (Scopus)

Abstract

Purpose:We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.Patients and Methods:In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.Results:Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).Conclusions:Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.

Original language	English
Article number	e67059
Journal	P L o S One
Volume	8
Issue number	6
Pages (from-to)	1-9
Number of pages	9
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0067059
Publication status	Published - 26 Jun 2013

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10.1371/journal.pone.0067059

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Schultz, N. A., Christensen, I. J., Werner, J., Giese, N., Jensen, B. V., Larsen, O., Bjerregaard, J. K., Pfeiffer, P., Calatayud, D., Nielsen, S. E., Yilmaz, M. K., Holländer, N. H., Wøjdemann, M., Bojesen, S. E., Nielsen, K. R., & Johansen, J. S. (2013). Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer. P L o S One, 8(6), 1-9. [e67059]. https://doi.org/10.1371/journal.pone.0067059

Schultz, NA, Christensen, IJ, Werner, J, Giese, N, Jensen, BV, Larsen, O, Bjerregaard, JK, Pfeiffer, P, Calatayud, D, Nielsen, SE, Yilmaz, MK, Holländer, NH, Wøjdemann, M, Bojesen, SE, Nielsen, KR & Johansen, JS 2013, 'Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer', P L o S One, vol. 8, no. 6, e67059, pp. 1-9. https://doi.org/10.1371/journal.pone.0067059

@article{0fa5fe14153748068dd9b3127d7456a2,

title = "Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer",

abstract = "Purpose:We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.Patients and Methods:In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.Results:Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).Conclusions:Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.",

author = "Schultz, {Nicolai A} and Christensen, {Ib Jarle} and Jens Werner and Nathalia Giese and Jensen, {Benny V} and Ole Larsen and Bjerregaard, {Jon K} and Per Pfeiffer and Dan Calatayud and Nielsen, {Svend E} and Yilmaz, {Mette Karen} and Holl{\"a}nder, {Niels H} and Morten W{\o}jdemann and Bojesen, {Stig E} and Nielsen, {Kaspar Rene} and Johansen, {Julia S}",

year = "2013",

month = jun,

day = "26",

doi = "10.1371/journal.pone.0067059",

language = "English",

volume = "8",

pages = "1--9",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "6",

}

TY - JOUR

T1 - Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

AU - Schultz, Nicolai A

AU - Christensen, Ib Jarle

AU - Werner, Jens

AU - Giese, Nathalia

AU - Jensen, Benny V

AU - Larsen, Ole

AU - Bjerregaard, Jon K

AU - Pfeiffer, Per

AU - Calatayud, Dan

AU - Nielsen, Svend E

AU - Yilmaz, Mette Karen

AU - Holländer, Niels H

AU - Wøjdemann, Morten

AU - Bojesen, Stig E

AU - Nielsen, Kaspar Rene

AU - Johansen, Julia S

PY - 2013/6/26

Y1 - 2013/6/26

N2 - Purpose:We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.Patients and Methods:In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.Results:Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).Conclusions:Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.

AB - Purpose:We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.Patients and Methods:In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.Results:Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).Conclusions:Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.

U2 - 10.1371/journal.pone.0067059

DO - 10.1371/journal.pone.0067059

M3 - Journal article

C2 - 23840582

SN - 1932-6203

VL - 8

SP - 1

EP - 9

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 6

M1 - e67059

ER -

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

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