Abstract

BackgroundAbnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).MethodsThe serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.ResultsThe median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called “double negative HCC”) exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.ConclusionOur findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.

Highlights

  • Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC)

  • Serum FGF19 levels The result of enzyme-linked immunosorbent assay (ELISA) demonstrated that the median serum FGF19 levels in controls, chronic liver disease (CLD) patients, and primary HCC patients were 78.8 pg/mL, 100.1 pg/mL, and

  • The FGF19 levels of HCC patients ranged from 20.0 pg/mL to 5605.8 pg/mL

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Summary

Introduction

Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). (AASLD), European Association for the Study of the Liver (EASL), and The Japan Society of Hepatology (JGH), these markers play a key role in monitoring for HCC onset and recurrence [6,7,8]. It is well-known that these markers often remain in the normal range, in small HCC [9]. Alternative serum biomarkers with high sensitivity and specificity are required

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