CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation

Kazufumi Honda, Verena A. Katzke, Anika Hüsing, Shinobu Okaya, Hirokazu Shoji, Kaoru Onidani, Anja Olsen, Anne Tjønneland, Kim Overvad, Elisabete Weiderpass, Paolo Vineis, David Muller, Kostas Tsilidis, Domenico Palli, Valeria Pala, Rosario Tumino, Alessio Naccarati, Salvatore Panico, Krasimira Aleksandrova, Heiner BoeingH. Bas Bueno-de-Mesquita, Petra H. Peeters, Antonia Trichopoulou, Pagona Lagiou, Kay Tee Khaw, Nick Wareham, Ruth C. Travis, Susana Merino, Eric J. Duell, Miguel Rodríguez-Barranco, María Dolores Chirlaque, Aurelio Barricarte, Vinciane Rebours, Marie Chiristine Boutron-Ruault, Francesca Romana Mancini, Paul Brennan, Ghislaine Scelo, Jonas Manjer, Malin Sund, Daniel Öhlund, Federico Canzian, Rudolf Kaaks

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1877-1887
Number of pages11
JournalInternational Journal of Cancer
Volume144
Issue number8
DOIs
Publication statusPublished - Apr 15 2019

Keywords

  • apolipoprotein A2
  • CA19-9
  • early detection
  • isoforms
  • pancreatic cancer
  • prospective study

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Honda, K., Katzke, V. A., Hüsing, A., Okaya, S., Shoji, H., Onidani, K., Olsen, A., Tjønneland, A., Overvad, K., Weiderpass, E., Vineis, P., Muller, D., Tsilidis, K., Palli, D., Pala, V., Tumino, R., Naccarati, A., Panico, S., Aleksandrova, K., ... Kaaks, R. (2019). CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. International Journal of Cancer, 144(8), 1877-1887. https://doi.org/10.1002/ijc.31900