Clinical Research Papers:

Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma

Kazuya Ofuji _, Keigo Saito, Shiro Suzuki, Manami Shimomura, Hirofumi Shirakawa, Daisuke Nobuoka, Yu Sawada, Mayuko Yoshimura, Nobuhiro Tsuchiya, Mari Takahashi, Toshiaki Yoshikawa, Yoshitaka Tada, Masaru Konishi, Shinichiro Takahashi, Naoto Gotohda, Yasunari Nakamoto and Tetsuya Nakatsura

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Oncotarget. 2017; 8:37835-37844. https://doi.org/10.18632/oncotarget.14271

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Kazuya Ofuji1,2,*, Keigo Saito1,*, Shiro Suzuki1, Manami Shimomura1, Hirofumi Shirakawa1, Daisuke Nobuoka1, Yu Sawada1, Mayuko Yoshimura1, Nobuhiro Tsuchiya1, Mari Takahashi1, Toshiaki Yoshikawa1, Yoshitaka Tada1, Masaru Konishi3, Shinichiro Takahashi3, Naoto Gotohda3, Yasunari Nakamoto2 and Tetsuya Nakatsura1

1Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan

2Second Department of Internal Medicine, University of Fukui, Eiheiji-cho Yoshida-gun, Fukui 910-1193, Japan

3Division of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan

*These authors have contributed equally to this work

Correspondence to:

Tetsuya Nakatsura, email: [email protected]

Keywords: hepatocellular carcinoma, glypican-3, tumor marker, enzyme-linked immunosorbent assay, recurrence

Received: March 23, 2016    Accepted: November 30, 2016    Published: December 27, 2016


Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface protein overexpressed in hepatocellular carcinoma(HCC), and its overexpression is associated with poor prognosis. The diagnostic potential of GPC3 as a serum marker has been reported. In the present study, we evaluated the usefulness of plasma GPC3 as a predictor for recurrence after surgical resection in stage I HCC patients by newly developed an enzyme-linked immunosorbent assay (ELISA) system. Current study demonstrated that high levels of preoperative plasma GPC3 patients tended to experience postoperative recurrence. On the other hand, pre- and postoperative plasma GPC3 positivity of non-recurrence patients was very low. Moreover, even after surgery, approximately half of patients who experienced recurrence were positive for plasma GPC3. Postoperative plasma GPC3 positivity was significantly correlated with worse recurrence-free survival. Immuohistochemical analysis also showed positive rate of GPC3-expression in HCC was higher in recurrence patients than in non-recurrence patients. These results suggested that both pre- and postoperative plasma GPC3 levels may be accurate predictors for recurrence after curative resection of early-stage HCC. It should be noted that the current study only examined a small number of cases; thus, a larger sample size is necessary to validate GPC3 as a predictor for HCC recurrence.

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