The Ion Channel Gene KCNAB2 Is Associated with Poor Prognosis and Loss of Immune Infiltration in Lung Adenocarcinoma

Abstract

The malignancy with the greatest global mortality rate is lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype. The evidence demonstrated that voltage-gated potassium channel subunit beta-2 (KCNAB2) significantly participated in the initiation of colorectal cancer and its progression. However, the biological function of KCNAB2 in LUAD and its effect on the tumor immune microenvironment are still unknown. In this study, we found that the expression of KCNAB2 in tissues of patients with LUAD was markedly downregulated, and its downregulation was linked to accelerated cancer growth and poor clinical outcomes. In addition, low KCNAB2 expression was correlated with a deficiency in immune infiltration. The mechanism behind this issue might be that KCNAB2 influenced the immunological process such that the directed migration of immune cells was affected. Furthermore, overexpression of KCNAB2 in cell lines promoted the expression of CCL2, CCL3, CCL4, CCL18, CXCL9, CXCL10, and CXCL12, which are necessary for the recruitment of immune cells. In conclusion, KCNAB2 may play a key function in immune infiltration and can be exploited as a predictive biomarker for evaluating prognosis and a possible immunotherapeutic target.

Role of pyroptosis-related cytokines in the prediction of lung cancer

“…MIP-1α, MIP-1β and MIP-2, as important chemokines, play pivotal role in attracting immune cells to tumor tissues sites [ 22 , 23 ]. However, other studies also found that higher expression of MIP-1α, MIP-1β or MIP-2 were also associated with poorer prognosis and decreased survival rate in lung adenocarcinoma patients [ [24] , [25] , [26] ]. High levels of MIP-1α have also been linked to promoting cancer cells growth and survival by stimulating tumor neovascularization [ 27 , 28 ].…”

KCNAB2 overexpression inhibits human non-small-cell lung cancer cell growth in vitro and in vivo

“…KCNAB2 mRNA and protein expression is significantly downregulated in immortalized NSCLC cell lines as well as in local NSCLC tissues when compared with human alveolar epithelial cells and corresponding adjacent normal tissues. Lyu et al, have shown that KCNAB2 expression is downregulated in lung adenocarcinoma [ 22 ]. The proliferation and migration ability of lung cancer cells was altered after KCNAB2 overexpression by plasmid transfection, although the difference is not statistically significant [ 22 ].…”

“…Lyu et al, have shown that KCNAB2 expression is downregulated in lung adenocarcinoma [ 22 ]. The proliferation and migration ability of lung cancer cells was altered after KCNAB2 overexpression by plasmid transfection, although the difference is not statistically significant [ 22 ]. However, in this study we confirmed that in different NSCLC cells, ectopic overexpression of KCNAB2 potently inhibited the cell malignant biological behaviors.…”

“…Lee et al, have found that Kvβ2, encoded by KCNAB2, is overexpressed in alveolar epithelial cells while promoting the clearance rate of the alveolar fluid [ 21 ]. Lyu et al, have demonstrated that lung adenocarcinoma patients with low KCNAB2 expression have poor prognosis [ 22 ]. However, the expression of KCNAB2 and its potential functions in human NSCLC have not been studied yet.…”

Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers

“…Kv subfamily A regulatory beta subunit 2 (KCNAB2) participates in neuroendocrine functions as well as in certain cancer processes [105]. Its low expression in LUAD is associated with accelerated tumor growth and poor prognosis, whereas its overexpression contributes to the expression of chemokines required for immune cell migration [104].…”