Des-γ-carboxyprothrombin (DCP) and NX-DCP expressions and their relationship with clinicopathological features in hepatocellular carcinoma.

Akiko Sumi,Osamu Nakashima,Jun Akiba,Toshi Abe,Masamichi Nakayama,Sakiko Sanada,Yoriko Nomura,Makiko Yasumoto,Hirohisa Yano,Sachiko Ogasawara,Joerg F Schlaak

doi:10.1371/journal.pone.0118452

Abstract

AimDes-γ-carboxyprothrombin (DCP) has been used as a tumor marker for hepatocellular carcinoma (HCC). Recently the DCP/NX-DCP ratio, calculated by dividing DCP by NX-DCP, has been reported useful in detecting HCC. The purpose of this study is to clarify the significance of DCP and NX-DCP expression in HCC tissues.MethodsHCC and non-HCC tissue samples were obtained from 157 patients and were immunohistochemically examined for DCP and NX-DCP expression using anti-DCP antibody and anti-NX-DCP antibody. DCP and NX-DCP expression scores were calculated by multiplying staining intensity grade by percentage of stained area. Serum DCP and NX-DCP levels were determined in 89 patients. We evaluated the relationship between tumor expression, serum level, and pathomorphological findings.ResultsIntrahepatic metastasis (im) was significantly more frequent in cases with high DCP expression than in cases with low DCP expression. High NX-DCP expression was associated with significantly lower histological grade, and less frequent im or portal vein invasion (vp) than low NX-DCP expression. Serum DCP was correlated with DCP expression, but serum NX-DCP was not correlated with NX-DCP expression. DCP-positive (≥40 mAU/L), NX-DCP-positive (≥90 mAU/L), and DCP/NX-DCP ratio-positive (≥1.5) cases were associated with significantly larger tumor size and more frequent vp than negative cases. DCP was rarely expressed, but NX-DCP was frequently expressed in non-cancerous liver tissues. Patients with NX-DCP expression-negative tumors showed a lower survival rate than those with NX-DCP expression-positive tumors (p = 0.04), whereas the survival in serum NX-DCP-positive cases was lower than that of serum negative cases (p = 0.02).ConclusionsDCP and NX-DCP were produced in HCC tissues, but differed in expression level and biological properties. DCP expression, serum DCP or NX-DCP level, and DCP/NX-DCP ratio were closely related to malignant properties of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world
Serum DCP was correlated with DCP expression, but serum NXDCP was not correlated with NX-DCP expression
DCP and NX-DCP were produced in HCC tissues, but differed in expression level and biological properties

Summary

Introduction

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. Des-γ-carboxyprothrombin (DCP), known as “protein induced by vitamin K absence or antagonist-II” (PIVKA-II), is an abnormal prothrombin that has been widely used as a tumor marker for HCC, and could be predictive of worse tumor behavior and prognosis [2,3,4,5]. It could be a preoperative predictor of poor prognosis in patients undergoing living donor liver plantation [5,6,7]. The purpose of this study is to clarify the significance of DCP and NX-DCP expression in HCC and non-cancerous tissues, and to analyze the relationship between serum DCP and NX-DCP levels and DCP and NX-DCP expression in HCC tissues

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Conclusion