J Cancer 2021; 12(9):2694-2701. doi:10.7150/jca.56436 This issue Cite

Research Paper

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma

Junjie Ao1*, Tetsuhiro Chiba1✉*, Hiroaki Kanzaki1, Kengo Kanayama1, Shuhei Shibata1, Akane Kurosugi1, Terunao Iwanaga1, Motoyasu Kan1, Takafumi Sakuma1, Na Qiang1, Yaojia Ma1, Ryuta Kojima1, Yuko Kusakabe1, Masato Nakamura1, Kazufumi Kobayashi1, Soichiro Kiyono1, Naoya Kanogawa1, Tomoko Saito1, Ryo Nakagawa1, Takayuki Kondo1, Sadahisa Ogasawara1, Eiichiro Suzuki1, Shingo Nakamoto1, Ryosuke Muroyama1, Akinobu Tawada1, Jun Kato1, Tatsuo Kanda2, Hitoshi Maruyama3, Naoya Kato1

1. Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
2. Department of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
3. Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
*These authors contributed equally to this work.

Citation:
Ao J, Chiba T, Kanzaki H, Kanayama K, Shibata S, Kurosugi A, Iwanaga T, Kan M, Sakuma T, Qiang N, Ma Y, Kojima R, Kusakabe Y, Nakamura M, Kobayashi K, Kiyono S, Kanogawa N, Saito T, Nakagawa R, Kondo T, Ogasawara S, Suzuki E, Nakamoto S, Muroyama R, Tawada A, Kato J, Kanda T, Maruyama H, Kato N. Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma. J Cancer 2021; 12(9):2694-2701. doi:10.7150/jca.56436. https://www.jcancer.org/v12p2694.htm
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Abstract

Graphic abstract

Hepatocellular carcinoma (HCC) is typically accompanied by abundant arterial blood flow. Although angiogenic growth factors such as Angiopoietin 2 (Ang2) play a central role in tumor angiogenesis in HCC, the role of serum Ang2 as a biomarker in HCC remains unclear. In this study, we aimed to investigate the potential of Ang2 as a diagnostic and prognostic biomarker in HCC using a sandwich enzyme-linked immunosorbent assay (ELISA). The median Ang2 levels in controls (n=20), chronic liver disease patients (n=98), and HCC patients (n=275) were 1.58, 2.33, and 3.53 ng/mL, respectively. The optimal cut-off value of Ang2 was determined as 3.5 ng/mL by receiver operating curve analysis. The sensitivity, specificity, and accuracy of Ang2 for HCC detection were 50.9, 83.7, and 59.5%, respectively. Spearman's rank correlation coefficient analysis demonstrated only a weak correlation between Ang2 serum levels and alpha-fetoprotein (AFP) or des-gamma-carboxy prothrombin (DCP) serum levels. The diagnostic value of Ang2 was comparable to those of other existing markers. In addition, 24 out of 73 patients with normal AFP and DCP levels (32.9%) demonstrated abnormally high Ang2 levels (≥3.5 ng/mL). Although no significant difference in overall survival was found between Ang2high and Ang2low patients with curative ablation therapy, recurrence-free survival (RFS) in Ang2high patients was observed to be significantly shorter than those in Ang2low patients. Multivariate analysis demonstrated that high serum Ang2 levels (≥3.5 ng/mL) and the presence of multiple tumors were poor prognostic factors. In conclusion, our findings indicate that serum Ang2 is a potential novel biomarker for both diagnosis and prognosis in HCC.

Keywords: Hepatocellular carcinoma, biomarker, angiopoietin 2, enzyme-linked immunosorbent assay


Citation styles

APA
Ao, J., Chiba, T., Kanzaki, H., Kanayama, K., Shibata, S., Kurosugi, A., Iwanaga, T., Kan, M., Sakuma, T., Qiang, N., Ma, Y., Kojima, R., Kusakabe, Y., Nakamura, M., Kobayashi, K., Kiyono, S., Kanogawa, N., Saito, T., Nakagawa, R., Kondo, T., Ogasawara, S., Suzuki, E., Nakamoto, S., Muroyama, R., Tawada, A., Kato, J., Kanda, T., Maruyama, H., Kato, N. (2021). Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma. Journal of Cancer, 12(9), 2694-2701. https://doi.org/10.7150/jca.56436.

ACS
Ao, J.; Chiba, T.; Kanzaki, H.; Kanayama, K.; Shibata, S.; Kurosugi, A.; Iwanaga, T.; Kan, M.; Sakuma, T.; Qiang, N.; Ma, Y.; Kojima, R.; Kusakabe, Y.; Nakamura, M.; Kobayashi, K.; Kiyono, S.; Kanogawa, N.; Saito, T.; Nakagawa, R.; Kondo, T.; Ogasawara, S.; Suzuki, E.; Nakamoto, S.; Muroyama, R.; Tawada, A.; Kato, J.; Kanda, T.; Maruyama, H.; Kato, N. Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma. J. Cancer 2021, 12 (9), 2694-2701. DOI: 10.7150/jca.56436.

NLM
Ao J, Chiba T, Kanzaki H, Kanayama K, Shibata S, Kurosugi A, Iwanaga T, Kan M, Sakuma T, Qiang N, Ma Y, Kojima R, Kusakabe Y, Nakamura M, Kobayashi K, Kiyono S, Kanogawa N, Saito T, Nakagawa R, Kondo T, Ogasawara S, Suzuki E, Nakamoto S, Muroyama R, Tawada A, Kato J, Kanda T, Maruyama H, Kato N. Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma. J Cancer 2021; 12(9):2694-2701. doi:10.7150/jca.56436. https://www.jcancer.org/v12p2694.htm

CSE
Ao J, Chiba T, Kanzaki H, Kanayama K, Shibata S, Kurosugi A, Iwanaga T, Kan M, Sakuma T, Qiang N, Ma Y, Kojima R, Kusakabe Y, Nakamura M, Kobayashi K, Kiyono S, Kanogawa N, Saito T, Nakagawa R, Kondo T, Ogasawara S, Suzuki E, Nakamoto S, Muroyama R, Tawada A, Kato J, Kanda T, Maruyama H, Kato N. 2021. Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma. J Cancer. 12(9):2694-2701.

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