Pan-Cancer Analyses Reveal Long Intergenic Non-Coding RNAs Relevant to Tumor Diagnosis, Subtyping and Prognosis

• LincRNAs exhibit significantly higher tissue specificities that mRNAs, which are then diminished in cancer tissues.
• LincRNAs are highly deregulated in cancers and their expression strongly correlates with molecular subtypes
• A panel of diagnostic lincRNA biomarkers are discovered using the pan-cancer samples of The Cancer Genome Atlas (TCGA), and further validated with multiple independent data sets.
• Knocking down experiments of some pan-cancer up-regulated lincRNAs slow down the cell growth and migration in some cancer cell lines, suggesting that lincRNAs may be biologically functional.Most of the work on cancer characterization, diagnosis, prognosis and treatment have been focused on the protein coding genes. Long intergenic non-coding RNAs (lincRNAs) are a relatively new class of RNA molecules that are understudied for their biological and clinical functions. This report aims to expand our understanding on the roles of lincRNA. Specifically, we demonstrate the relevance of lincRNAs to tumor diagnosis, subtyping and prognosis. We further propose a panel of lincRNAs as potentially robust pan-cancer diagnostic biomarkers.

Long intergenic noncoding RNAs (lincRNAs) are a relatively new class of non-coding RNAs that have the potential as cancer biomarkers. To seek a panel of lincRNAs as pan-cancer biomarkers, we have analyzed transcriptomes from over 3300 cancer samples with clinical information. Compared to mRNA, lincRNAs exhibit significantly higher tissue specificities that are then diminished in cancer tissues. Moreover, lincRNA clustering results accurately classify tumor subtypes. Using RNA-Seq data from thousands of paired tumor and adjacent normal samples in The Cancer Genome Atlas (TCGA), we identify six lincRNAs as potential pan-cancer diagnostic biomarkers (PCAN-1 to PCAN-6). These lincRNAs are robustly validated using cancer samples from four independent RNA-Seq data sets, and are verified by qPCR in both primary breast cancers and MCF-7 cell line. Interestingly, the expression levels of these six lincRNAs are also associated with prognosis in various cancers. We further experimentally explored the growth and migration dependence of breast and colon cancer cell lines on two of the identified lncRNAs. In summary, our study highlights the emerging role of lincRNAs as potentially powerful and biologically functional pan-cancer biomarkers and represents a significant leap forward in understanding the biological and clinical functions of lincRNAs in cancers.