Background
More than half of non-small cell lung cancer (NSCLC) patients present with metastatic disease at initial diagnosis with an estimated five-year survival rate of ~5%. Despite advances in understanding primary lung cancer oncogenesis metastatic disease remains poorly characterized. Recent studies demonstrate important roles of long non-coding RNAs (lncRNAs) in tumor physiology and as prognostic markers. Therefore, we present the first transcriptome analysis to identify lncRNAs altered in metastatic lung adenocarcinoma leading to the discovery and characterization of the lncRNA LCAL62 as a prognostic biomarker. Patients and
Conclusion
We discovered that LCAL62 was down-regulated in lung cancer progression to promote invasive phenotypes, and lower expression was significantly associated with poor patient outcome and aggressive lung adenocarcinoma.
Methods
RNA-Seq, microarray, nanoString expression, and clinical data from 1,116 LUAD patients across six independent cohorts and 83 LUAD cell lines were used to discover and evaluate the survival association of metastasis associated lncRNAs. Coexpression and gene set enrichment analyses were used to establish gene regulatory networks and implicate metastasis associated lncRNAs in specific biological processes.
Results
Our integrative analysis discovered LCAL62 as the most down-regulated lncRNA in metastasis. Further low LCAL62 expression promoted aggressive phenotypes and regulated genes associated with metastasis (such as metastasis repressor FOXA2). Low LCAL62 expression corresponded to poor overall patient survival across five independent lung adenocarcinoma cohorts (n = 881) including our own nanoString validation cohort.