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Expression and Malignant Potential of B4GALNT4 in Esophageal Squamous Cell Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

β-1,4-N-Acetyl-galactosaminyltransferase 4 (B4GALNT4), an enzyme involved in ganglioside synthesis, is upregulated in many cancers. We examine B4GALNT4 expression and its relationship to prognosis in esophageal squamous cell carcinoma (ESCC).

Patients and Methods

Expression of B4GALNT4 mRNA and B4GALNT4 protein was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively, in 17 human ESCC cell lines and/or clinical specimens from two independent cohorts of 147 and 159 ESCC patients. The contributions of B4GALNT4 to proliferation, invasion, migration, and adhesion was evaluated in ESCC cells subjected to siRNA-mediated gene knockdown. Correlations between clinicopathological parameters and B4GALNT4 expression in clinical specimens were analyzed in both patient cohorts.

Results

B4GALNT4 mRNA expression levels varied widely in ESCC cell lines, regardless of differentiation status or the originating tissue. Knockdown of B4GALNT4 significantly suppressed the proliferation, invasion, migration, and adhesion of ESCC cell lines compared with control cells. B4GALNT4 mRNA was overexpressed in ESCC tissues compared with adjacent normal esophageal tissues. High mRNA expression was significantly associated with poor disease-free survival and hematogenous recurrence, and high B4GALNT4 protein expression was also significantly related to poor disease-specific survival. On multivariable analysis, high B4GALNT4 expression was an independent predictor of poor prognosis. In both patient cohorts, high B4GALNT4 expression did not correlate with known prognostic factors, such as disease stage, lymphovascular invasion, or squamous cell-carcinoma-related antigen level.

Conclusions

B4GALNT4 influences the malignant behavior of ESCC cells. B4GALNT4 expression may serve as a novel prognostic marker, independent of established risk factors, for ESCC patients.

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Acknowledgment

We thank Anne M. O’Rourke, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan

    Hayato Baba MD & Tsutomu Fujii MD, PhD, FACS

  2. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    Hayato Baba MD, Mitsuro Kanda MD, PhD, FACS, Koichi Sawaki MD, PhD, Dai Shimizu MD, PhD, Masahiko Koike MD, PhD & Yasuhiro Kodera MD, PhD, FACS

  3. Department of Thoracic Surgery, Akita University Graduate School of Medicine, Akita, Japan

    Yusuke Sato MD, PhD & Satoru Motoyama MD, PhD

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  1. Hayato Baba MD
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  2. Mitsuro Kanda MD, PhD, FACS
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  3. Yusuke Sato MD, PhD
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  4. Koichi Sawaki MD, PhD
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  5. Dai Shimizu MD, PhD
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  6. Masahiko Koike MD, PhD
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  8. Yasuhiro Kodera MD, PhD, FACS
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  9. Tsutomu Fujii MD, PhD, FACS
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Correspondence to Mitsuro Kanda MD, PhD, FACS.

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Baba, H., Kanda, M., Sato, Y. et al. Expression and Malignant Potential of B4GALNT4 in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 27, 3247–3256 (2020). https://doi.org/10.1245/s10434-020-08431-8

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  • DOI: https://doi.org/10.1245/s10434-020-08431-8

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