Identification of recurrence-associated microRNAs in stage I lung adenocarcinoma

Abstract

Lung cancer is the most common cause of cancer-associated death worldwide. Postoperative relapse and subsequent metastasis result in a high mortality rate, even in early stage lung cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and are frequently dysregulated in various cancers. The aim of this study was to identify recurrence-associated miRNAs in early stage lung cancer. To screen for differentially expressed miRNAs related to postoperative recurrence, miRNA microarray data derived from stage I lung adenocarcinoma formalin-fixed paraffin-embedded (FFPE) tissue samples (n=6) and publically available the Cancer Genome Atlas (TCGA) data were analyzed. An independent sample (n=29) was used to validate candidate miRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). In miRNA expression profiling, we identified 60 significantly dysregulated miRNAs in the relapsed group. Additionally, 20 dysregulated miRNAs were found using TCGA data set. Three miRNAs (let-7g-5p, miR-143-3p, and miR-374a-5p) were associated with postoperative recurrence in both microarray and TCGA data sets. All 3 candidate miRNAs were validated in the independent cohort of stage I adenocarcinoma by qRT-PCR. We discovered 3 recurrence-associated miRNAs of stage I lung adenocarcinoma samples using FFPE tissue, which showed possible clinical utility as biomarkers predicting recurrence after curative surgery. Further investigation of the functional properties of these miRNAs is needed.