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KCNJ15 Expression and Malignant Behavior of Esophageal Squamous Cell Carcinoma

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Abstract

Background

We aimed to clarify the role of potassium voltage-gated channel subfamily J member 15 (KCNJ15) in esophageal squamous cell carcinoma (ESCC) cells and its potential as a prognosticator in ESCC patients.

Methods

KCNJ15 transcription levels were evaluated in 13 ESCC cell lines and polymerase chain reaction (PCR) array analysis was conducted to detect coordinately expressed genes with KCNJ15. The biological functions of KCNJ15 in cell invasion, proliferation, migration, and adhesion were validated through small interfering RNA-mediated knockdown experiments. Cell proliferation was further evaluated through the forced expression experiment. KCNJ15 expression was detected in 200 ESCC tissues by quantitative real-time reverse transcription PCR (qRT-PCR) and analyzed in 64 representative tissues by immunohistochemistry. Correlations between KCNJ15 expression levels and clinicopathological features were also analyzed.

Results

The KCNJ15 expression levels varied widely in ESCC cell lines and correlated with COL3A1, JAG1, and F11R. Knockdown of KCNJ15 expression significantly repressed cell invasion, proliferation, and migration of ESCC cells in vitro. Furthermore, overexpression of KCNJ15 resulted in increased cell proliferation. Patients were stratified using the cut-off value of KCNJ15 messenger RNA (mRNA) levels in 200 ESCC tissues using receiver operating characteristic curve analysis; the high KCNJ15 expression group had significantly shorter overall and disease-free survival times. In multivariable analysis, high expression of KCNJ15 was identified as an independent poor prognostic factor. Staining intensity of in situ KCNJ15 protein expression tended to be associated with KCNJ15 mRNA expression levels.

Conclusions

KCNJ15 is involved in aggressive tumor phenotypes of ESCC cells and its tissue expression levels may be useful as a prognosticator of patients with ESCC.

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Correspondence to Mitsuro Kanda MD, PhD, FACS.

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Shunsuke Nakamura, Mitsuro Kanda, Masahiko Koike, Dai Shimizu, Shinichi Umeda, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Kenji Omae, and Yasuhiro Kodera have no commercial interests to declare. No sources of financial or material support were used in the preparation of this study.

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Nakamura, S., Kanda, M., Koike, M. et al. KCNJ15 Expression and Malignant Behavior of Esophageal Squamous Cell Carcinoma. Ann Surg Oncol (2020). https://doi.org/10.1245/s10434-019-08189-8

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