TY - JOUR
T1 - CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer
T2 - a prospective evaluation
AU - Honda, Kazufumi
AU - Katzke, Verena A.
AU - Hüsing, Anika
AU - Okaya, Shinobu
AU - Shoji, Hirokazu
AU - Onidani, Kaoru
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Overvad, Kim
AU - Weiderpass, Elisabete
AU - Vineis, Paolo
AU - Muller, David
AU - Tsilidis, Kostas
AU - Palli, Domenico
AU - Pala, Valeria
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Panico, Salvatore
AU - Aleksandrova, Krasimira
AU - Boeing, Heiner
AU - Bueno-de-Mesquita, H. Bas
AU - Peeters, Petra H.
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Travis, Ruth C.
AU - Merino, Susana
AU - Duell, Eric J.
AU - Rodríguez-Barranco, Miguel
AU - Chirlaque, María Dolores
AU - Barricarte, Aurelio
AU - Rebours, Vinciane
AU - Boutron-Ruault, Marie Chiristine
AU - Romana Mancini, Francesca
AU - Brennan, Paul
AU - Scelo, Ghislaine
AU - Manjer, Jonas
AU - Sund, Malin
AU - Öhlund, Daniel
AU - Canzian, Federico
AU - Kaaks, Rudolf
N1 - Funding Information:
Key words: pancreatic cancer, early detection, CA19-9, apolipoprotein A2, isoforms, prospective study Abbreviations: AUC: Area under the curve; EPIC: European Prospective Investigation into Cancer; EUS: Endoscopic ultrasonography; IPMN: Intraductal papillary mucinous neoplasia; NCI EDRN: US National Cancer Center Early Detection Research Network; PDAC: Pancreatic ductal adenocarcinomas; ROC: Receiver operating characteristic; UKCTOCS: UK Collaborative Trial of Ovarian Cancer Screening Additional Supporting Information may be found in the online version of this article. K.H. and V.A.K. contributed equally to this work Conflict of interest: The authors declare no conflict of interest and no specific disclosures to be made. Kazufumi Honda is coinventor of a patent, held by Tokyo National Cancer Center Research Institute and Tory company, for the use of “apolipoprotein-A2 isoforms” for early detection of pancreatic disease. Grant sponsor: Practical Research for Innovative Cancer Control; Grant numbers: 18ck0106280h0002; Grant sponsor: Project for Cancer Research and Therapeutic Evolution (P-CREATE); Grant sponsor: Japan Agency for Medical Research and Development. DOI: 10.1002/ijc.31900 History: Received 21 Feb 2018; Accepted 13 Jul 2018; Online 27 Sep 2018 Correspondence to: Rudolf Kaaks, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, Tel.: +49 6221 422219, Fax: ++49 6221 42 2203; E-mail: [email protected]; or Kazufumi Honda; Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, 104-0045 Tokyo, Japan, Tel.: +81 3 3542 2511, Fax: ++81 3 3547 6045, E-mail: [email protected]
Publisher Copyright:
© 2018 UICC
PY - 2019/4/15
Y1 - 2019/4/15
N2 - Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform (“ApoA2-ATQ/AT”), alone and in combination with carbohydrate antigen 19–9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6–18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6–18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6–18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.
AB - Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform (“ApoA2-ATQ/AT”), alone and in combination with carbohydrate antigen 19–9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6–18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6–18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6–18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.
KW - apolipoprotein A2
KW - CA19-9
KW - early detection
KW - isoforms
KW - pancreatic cancer
KW - prospective study
KW - Pancreas/diagnostic imaging
KW - Predictive Value of Tests
KW - Prospective Studies
KW - Enzyme-Linked Immunosorbent Assay
KW - Humans
KW - Middle Aged
KW - CA-19-9 Antigen/blood
KW - Male
KW - Case-Control Studies
KW - Early Detection of Cancer/methods
KW - Time Factors
KW - Pancreatic Neoplasms/blood
KW - Protein Isoforms/analysis
KW - Adult
KW - Female
KW - ROC Curve
KW - Aged
KW - Apolipoprotein A-II/blood
UR - https://www.scopus.com/pages/publications/85058028091
U2 - 10.1002/ijc.31900
DO - 10.1002/ijc.31900
M3 - Article
C2 - 30259989
AN - SCOPUS:85058028091
SN - 0020-7136
VL - 144
SP - 1877
EP - 1887
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 8
ER -