Abstract
Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts.
Highlights
Worldwide, lung cancer is the leading cancer killer, and the overall 5-year survival is only 15% [1]
We first explored the difference in gene expression between normal and tumor tissues in lung adenocarcinoma in the TWN cohort
We compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma
Summary
Lung cancer is the leading cancer killer, and the overall 5-year survival is only 15% [1]. 98% of lung cancers are carcinomas that arise from epithelial cells [2]. Lung carcinomas are generally categorized into non-small cell and small cell lung cancers by the size and appearance of the malignant cells. About 80% of lung cancers are non-small cell cancers, and of these, roughly 50% are adenocarcinomas [2], which usually originate in peripheral lung tissue. Lung adenocarcinoma is strongly associated with smoking [3], which has become the most common major type of lung cancer in smokers compared to squamous cell carcinoma. Adenocarcinoma is the type of lung cancer most commonly seen in non-smokers and women [4,5]
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