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. 2019 Apr 15;144(8):1877-1887.
doi: 10.1002/ijc.31900. Epub 2018 Dec 4.

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

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

Kazufumi Honda et al. Int J Cancer. .

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.

Keywords: CA19-9; apolipoprotein A2; early detection; isoforms; pancreatic cancer; prospective study.

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Conflict of interest statement

Conflicts of interest: The authors declare no conflict of interest and no specific disclosures to be made. Kazufumi Honda is co-inventor 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.

Figures

Figure 1
Figure 1. Box and whisker plots showing plasma levels of CA19-9 and ApoA2-ATQ/AT for pancreatic cancer cases and matched controls, by intervals of time from blood donation till diagnosis of (matched) case.
Figure 2
Figure 2. ROC curves and C-statistics for blood samples taken ≤6 months, >6-18 months, >18-36 months and >36-60 months before cancer diagnosis.

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