Can long non-coding RNAs reveal the hidden code of lung cancer?

© Non-coding RNA Investigation. All rights reserved. Non-coding RNA Investig 2020;4:6 | http://dx.doi.org/10.21037/ncri.2020.03.04 At present, lung cancer remains the first cause of cancerrelated death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80% of cases. Despite advances in the treatment of NSCLC, patient prognosis remains dismal, with overall survival rates ranging from 55% in local disease to 4% in metastatic disease. This scenario, combined with the absence of proper screening tools, highlights the urgency of developing new diagnostic biomarkers that can identify lung cancer patients at early-stage where surgery with curative intent is the preferred treatment. Although early diagnosis is related to increased survival, in the first five years after surgery, up to 40% of resected patients relapse (1). Therefore, it also urges the development of new biomarkers to identify lung cancer patients with a high risk of relapse after surgery in order to improve their clinical management and survival. In this line, the study of long non-coding RNAs (lncRNAs) has emerged as one of the most promising fields in the development of new biomarkers for all cancer types, including NSCLC (2-4). LncRNAs display an extremely specific expression pattern, and their capacity to discriminate between tumor and normal tissue is superior to coding genes or pseudogenes, making them an ideal source of biomarkers (5). The recently published manuscript by Acha-Sagredo et al. reports their study of deregulated lncRNAs associated with NSCLC pathogenesis (6) and provides some additional information to the state of the art (2-4). This was twophase study (Figure 1). An initial discovery data set based on microarray analysis of 44 paired normal and NSCLC tissue was used for the identification of dysregulated lncRNAs in NSCLC. This discovery phase was followed by qPCR validation in 38 additional specimens, which was cross-validated using available TCGA data [n=850: lung adenocarcinoma (LUAD) =585; squamous cell carcinoma (LUSC) =504]. During the discovery phase, a total of 1122 downregulated and 771 upregulated lncRNAs [including long intergenic non-coding RNAs (lincRNAs) and antisense transcripts] were identified. The validation phase confirmed the upregulation of six lncRNAs and the downregulation of six other lncRNAs in tumor tissue compared to normal tissue. Some of the upregulated lncRNAs identified have previously been described as oncogenes in NSCLC. For example, LINC00673 and PCAT6 have been linked to several key processes in cancer progression: LINC00673 to epithelial-to-mesenchymal transition (EMT) and cellular senescence (7,8); and PCAT6 to the recruiting of chromatinmodifying complexes (9). Consistent with these results, some of the downregulated lncRNAs identified in the study by Acha-Sagredo et al. (6) have previously been described by Salavaty et al. using TCGA LUAD data (10). For instance, they explored and confirmed the role of the lncRNAs LANCL1-AS1, FENDRR, LINC00968 and ADAMTS9-AS2 as tumor suppressors in NSCLC adenocarcinoma. Salavaty et al. analyzed the TCGA data using two different webEditorial Commentary