FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of cholangiocarcinoma in patients with primary sclerosing cholangitis

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• 作者：Andreas Wannhoff ; Johannes Roksund Hov ; Trine Folseraas ; Christian Rupp ; Kilian Friedrich ; Jarl Andreas Anmarkrud ; Karl Heinz Weiss ; Peter Sauer ; Peter Schirmacher ; Kirsten Muri Boberg ; Wolfgang Stremmel ; Tom Hemming Karlsen ; Daniel Nils Gotthardt
• 关键词：PSC ; primary sclerosing cholangitis ; CCA ; cholangiocarcinoma ; GBCA ; gallbladder carcinoma ; CA19-9 ; carbohydrate antigen 19-9 ; FUT2 ; fucosyltransferase 2 ; FUT3 ; fucosyltransferase 3 ; IBD ; inflammatory bowel disease ; MELD ; Model of End-Stage Liver Disease ; LT ; liver transplantation ; SNP ; single-nucleotide polymorphism ; WGA ; whole-genome amplified ; ROC ; receiver operating characteristic ; IQR ; inter-quartile range ; AUC ; area under the curve ; PPV ; positive predictive value ; NPV ; negative predictive v
• 刊名：Journal of Hepatology
• 出版年：December, 2013
• 年：2013
• 卷：59
• 期：6
• 页码：1278-1284
• 全文大小：1008 K

文摘

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Background & Aims

Allelic variants of fucosyltransferases 2 and 3 (FUT2/3) influence serum levels of CA19-9, a screening parameter commonly used for detection of biliary malignancy in PSC. We aimed at improving diagnostic accuracy of CA19-9 by determining the impact of FUT2/3 genotypes.

Methods

CA19-9 levels were measured in 433 PSC patients, 41 of whom had biliary malignancy. Genotypes for FUT3 and FUT2 were used to assign patients to one of three groups: A, no FUT3 activity regardless of FUT2 activity; B, both FUT2 and FUT3 activity and C, no FUT2 activity without loss of FUT3 activity. Group-specific cut-off values were determined by Youden鈥檚 index.

Results

The median CA19-9 values of cancer-free patients were significantly different (p <0.001) in Groups A (2.0 U/ml), B (17.0 U/ml), and C (37.0 U/ml). Biliary malignancy patients in Groups B and C had significantly higher CA19-9 values than cancer-free patients (p <0.001). The optimal cut-off, as determined by ROC analysis, for all patients was 88.5 U/ml. Optimal cut-off values in Groups A, B, and C were 4.0 U/ml, 74.5 U/ml, and 106.8 U/ml, respectively. Use of these values improved sensitivity of CA19-9 in Groups B and C. Further, use of group-dependent cut-off values with 90% sensitivity resulted in a 42.9% reduction of false positive results.

Conclusions

Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity and reduced the number of false positive results.