Korean J Physiol Pharmacol.  2019 Nov;23(6):529-537. 10.4196/kjpp.2019.23.6.529.

Expression of potassium channel genes predicts clinical outcome in lung cancer

• Ko EA
• Kim YW
• Lee D
• Choi J
• Kim S
• Seo Y
• Bang H
• Kim JH
• Ko JH

• KMID: 2461046
• DOI: http://doi.org/10.4196/kjpp.2019.23.6.529

Abstract

Lung cancer is the most common cause of cancer deaths worldwide and several molecular signatures have been developed to predict survival in lung cancer. Increasing evidence suggests that proliferation and migration to promote tumor growth are associated with dysregulated ion channel expression. In this study, by analyzing high-throughput gene expression data, we identify the differentially expressed K⁺ channel genes in lung cancer. In total, we prioritize ten dysregulated K⁺ channel genes (5 up-regulated and 5 down-regulated genes, which were designated as K-10) in lung tumor tissue compared with normal tissue. A risk scoring system combined with the K-10 signature accurately predicts clinical outcome in lung cancer, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node involvement, tumor size, and tumor grade. We further indicate that the K-10 potentially predicts clinical outcome in breast and colon cancers. Molecular signature discovered through K⁺ gene expression profiling may serve as a novel biomarker to assess the risk in lung cancer.

Keyword

Biomarker; Gene expression; K⁺ channel; Lung cancer; Molecular signature

MeSH Terms

Breast
Colonic Neoplasms
Gene Expression
Gene Expression Profiling
Humans
Ion Channels
Lung Neoplasms*
Lung*
Lymph Nodes
Potassium Channels*
Potassium*
Ion Channels
Potassium
Potassium Channels

Figure

• 

  Fig. 1 Distribution of expression level for the K-10 signature in the Italian cohort (GSE10072). The 10 dysregulated genes were verified in the Taiwanese cohort (GSE19804), among which 5 genes (6 probe sets, the upper row) were up-regulated while 5 genes (7 probe sets, the lower row) were down-regulated in tumor tissue. Each panel was labelled with the corresponding gene symbol and probeset ID. Y-axis: log2 transformed expression level. The solid line depicts the mean of expression value for normal or tumor tissue. The dot line indicates the overall mean of expression value across all individual samples.

• 

  Fig. 2 Heatmap of expression level for the K-10 signature. (A) Heatmap of expression level for the K-10 signature in the Italian cohort (GSE10072). 6 probe sets represent 5 up-regulated genes and 7 probe sets represent 5 down-regulated genes. Each row was labelled with the corresponding gene symbol and probe set ID. “++”: tumor tissue; “−”: normal tissue. (B) Heatmap of expression level for the K-10 signature in the Taiwanese cohort (GSE19804). 15 probe sets encoding 5 up-regulated and 5 down-regulated genes were displayed. Each row was labelled with the corresponding gene symbol and probe set ID. “++”: tumor tissue; “−”: normal tissue.

• 

  Fig. 3 Kaplan-Meier curves for the patients from the training and validation cohorts. The expression of K-10 signature predicts poor clinical outcome in lung cancer. High-score patients were defined as those having a K-10 risk score greater than or equal to the group median score. p-value were calculated by log-rank tests for the differences in overall survival between the high-score and low-score groups.

• 

  Fig. 4 Kaplan-Meier survival curves of the lung cancer patients grouped by clinicopathologic factors. K-10 is independent from other clinicopathologic factors in lung cancer. (A) Patients were stratified by age; (B) Patients were stratified by lymph node status; and (C) Patients were stratified by tumor size. High-score patients were defined as those having a K-10 risk score greater than or equal to the group median score. p-value were calculated by log-rank tests for the differences in overall survival between the high-score and low-score groups.

• 

  Fig. 5 Kaplan-Meier curves for the patients from the training and validation cohorts in breast and colon cancers. The expression-of K-10 signature predicts poor clinical outcome in both (A) breast and (B) colon cancers. High-score patients were defined as those having a K-10 risk score greater than or equal to the group median score. p-values were calculated by log-rank tests for the differences in overall survival between the high-score and low-score groups.

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