Plasma vasohibin-1 and vasohibin-2 are useful biomarkers in patients with esophageal squamous cell carcinoma

Abstract

Background

Vasohibins (VASH), which are angiogenesis regulators, consist of Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2). VASH1 is an angiogenesis inhibitor, while VASH2 is a proangiogenic factor. Patients with esophageal squamous cell carcinoma (ESCC) with high tumor expression levels of VASH1 and VASH2 have been reported to show a poor prognosis. The clinical significance of VASH concentrations in the blood of patients with ESCC has not yet been investigated.

Methods

Plasma samples from 89 patients with ESCC were analyzed, and the relationships between the plasma VASH concentrations and the clinicopathological factors of the patients were evaluated. Immunohistochemical examination (IHC) of the resected tumor specimens for VASH was performed in 56 patients, and the correlation between the plasma VASH concentrations and tumor expression levels of VASH was analyzed.

Results

The patient group with high plasma concentrations of VASH1 showed a higher frequency of lymph node metastasis (P = 0.01) and an invasive growth pattern (P = 0.05). Furthermore, poorly differentiated cancer occurred at a higher frequency in the patient group with high plasma concentrations of VASH2 (P < 0.01). High tumor expression levels of VASH1 were encountered more frequently in the patient group with high plasma concentrations of VASH1 (P = 0.03), and high tumor expression levels of VASH2 were encountered more frequently in the patient group with high plasma concentrations of VASH2 (P = 0.04).

Conclusions

In patients with ESCC, high plasma concentrations were associated with poor clinical outcomes for both VASH1 and VASH2. We propose that results indicate that plasma VASH1 and VASH2 are useful biomarkers in patients with ESCC.

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Acknowledgements

For this research, the anti-vasohibin antibodies were provided by the Institute of Development, Aging and Cancer, Tohoku University, and we are grateful to Dr. Yasuhiro Suzuki and Professor Yasufumi Sato for their discussions about vasohibin. This research was supported by the Support Center for Medical Research and Education of Tokai University School of Medicine. We thank Mr. Hideo Tsukamoto (Japan Medical Device Technology), Mr. Noboru Kawabe and Ms. Yoko Kameyama for there suppport with research. We thank Ms. Izu Inada and Ms. Izumi Tsuchiya (Department of Gastroenterological Surgery, Tokai University School of Medicine) for their support with the data analysis.

Funding

The present study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant no. 17K10609).

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Correspondence to Soji Ozawa.

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Ethical Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

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The authors declare that have no competing interests.

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Yamamoto, M., Ozawa, S., Ninomiya, Y. et al. Plasma vasohibin-1 and vasohibin-2 are useful biomarkers in patients with esophageal squamous cell carcinoma. Esophagus 17, 289–297 (2020). https://doi.org/10.1007/s10388-020-00719-8

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Keywords

  • Esophageal cancer
  • Vasohibin-1
  • Vasohibin-2
  • Plasma concentration
  • Biomarker