Biomarker potential of repetitive-element transcriptome in lung cancer

Since repetitive elements (REs) account for nearly 53% of the human genome, profiling its transcription after an oncogenic change might help in the search for new biomarkers. Lung cancer was selected as target since it is the most frequent cause of cancer death. A bioinformatic workflow based on well-established bioinformatic tools (such as RepEnrich, RepBase, SAMTools, edgeR and DESeq2) has been developed to identify differentially expressed RNAs from REs. It was trained and tested with public RNAseq data from matched sequencing of tumour and healthy lung tissues from the same patient to reveal differential expression within the RE transcriptome. Healthy lung tissues express a specific set of REs whose expression, after an oncogenic process, is strictly and specifically changed. Discrete sets of differentially expressed REs were found for lung adenocarcinoma, for small-cell lung cancer, and for both cancers. Differential expression affects more HERV-than LINE-derived REs and seems biased towards down-regulation in cancer cells. REs behaving consistently in all patients were tested in a different patient cohort to validate the proposed biomarkers. Down-regulation of AluYg6 and LTR18B was confirmed as potential lung cancer biomarkers, while upregulation of HERVK11D-Int is specific for lung adenocarcinoma and up-regulation of UCON88 is specific for small cell lung cancer. Hence, the study of RE transcriptome might be considered another research target in cancer, making REs a promising source of lung cancer biomarkers.