Abstract
Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9–9% of total lung cancers. Recently, RNA-seq based studies have revealed major genomic aberrations in LCLC. In this study, we aim to identify long non-coding RNAs (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile of LCLC and other non-small cell lung carcinoma (NSCLC) was downloaded from Gene Expression Omnibus (GEO) and analyzed. Using 10 LCLC samples, we found that 18% of all the annotated LncRNAs are expressed in LCLC samples. Among 1794 expressed LncRNAs, 11 were overexpressed and 14 were downregulated in LCLC compared to normal samples. Based on receiver operating characteristic (ROC) analysis, we showed that the top five differentially expressed LncRNAs were able to differentiate between LCLC and normal samples with high sensitivity and specificity. Guilt by association analysis using genes correlating with differentially expressed LncRNAs identified several cancer-associated pathways, suggesting the role of these deregulated LncRNA in LCLC biology. We also identified the LncRNA differentially expressed in LCLC compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD). We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD. Interestingly, LCLC had more downregulated LncRNA compared to LUAD and LUSC. Our study provides novel insight into LncRNA deregulation in LCLC. This study also finds tools to diagnose LCLC and differentiate LCLC with other Non-Small Cell Lung Cancer.
Highlights
Lung cancer is the major cause of cancer-related deaths worldwide [1] and is generally divided into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) [2]
We identified the long non-coding RNAs (LncRNAs) differentially expressed in large cell carcinoma (LCLC) compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD)
We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD
Summary
Lung cancer is the major cause of cancer-related deaths worldwide [1] and is generally divided into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) [2]. Non-small cell lung carcinoma is further divided into lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and undifferentiated large cell carcinoma (LCLC) [3]. Lung-adenocarcinoma, LUSC, and SCLC are well-defined based on genetic and epigenetic studies; LCLC is not as well studied and is characterized as undifferentiated [3]. As a result of recent advancements in high-throughput sequencing techniques, a large part of these non-coding regions has been demonstrated to be actively transcribed [6]. The proportion of these actively transcribed non-coding regions increases with genomic complexity, suggesting the potentially important role of these previously uncharacterized genomic regions [7]. The transcriptions with no protein coding potential are called non-coding RNA, and non-coding RNA of 200 nt in length are called long non-coding RNA
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