Functions and clinical significance of KCNB1 in esophageal squamous cell carcinoma.

Abstract

Background: Voltage-gated potassium channel subfamily B member 1 (KCNB1) encodes the α-subunit of the Kv2.1 channel and mediates transmembrane potassium transport. The functions and mechanisms underlying KCNB1 activation have been examined in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, the present study investigated the involvement of KCNB1 in tumor progression and the clinicopathological significance of its expression in ESCC.

Methods: Knockdown experiments using KCNB1 small interfering RNA were performed on the human ESCC cell lines, KYSE70 and TE5, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. Gene expression profiles were examined using a microarray analysis. An immunohistochemical (IHC) analysis was performed on 129 primary tumor samples from ESCC patients who underwent curative esophagectomy.

Results: Cell proliferation, G₂-M phase progression, migration, and invasion were inhibited, and apoptosis was induced in KCNB1-depleted cells. Microarray results showed that KCNB1 gene expression affected Ephrin receptor signaling by suppressing EPHB1, EPHB2, and ERK1/2 gene expression. IHC results revealed a relationship between high KCNB1 expression and a poor prognosis. High KCNB1 expression was extracted as an independent prognostic factor in a multivariate analysis of 5-year relapse-free survival in ESCC patients (p = 0.0197).

Conclusions: Cell proliferation is controlled by KCNB1 through its regulation of ERK1/2 gene expression via ephrin receptor signaling. A relationship was observed between KCNB1 and the prognosis of ESCC patients, indicating its potential as a biomarker for cancer progression and in targeted therapy for ESCC.