Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers

Abstract

Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.Cancer Res; 76(2); 216-26. Ó2015 AACR.

Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing

“…Furthermore, a study conducting a pan-cancer investigation noticed that promoters containing SINE, LINE, and LTRs were upregulated in cancers (38). In our study and in concordance with previous studies, we observed that the majority of LTR and LINE elements were upregulated in EAC.…”

“…In our study and in concordance with previous studies, we observed that the majority of LTR and LINE elements were upregulated in EAC. Our study also confirms the upregulation of REP522, which has previously been indicated in cancer (38). What differs from previous studies is that we observed a downregulation of SINE in EAC.…”

“…5B). This latter finding is especially interesting as we also found that APOBEC3G, an inhibitor of SINE elements (37) (38). In Figure 4.…”

Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC

“…The overlapping genes included TOP2A, which is upregulated across multiple cancer types (15,40), and six kinases including AURKA and AURKB that are implicated in various cancer types (41). Among 22 epi-markers, IGF2BP3 and CEP55 (associated with poor survival in LUAD as described before) showed highest correlations with the cell-cycle genes (Supplementary Fig.…”

“…The thresholds of absolute fold change > 2 and FDR < 0.05 were used. We also evaluated the expression status in binary fashion: ON (expressed, count > 0), OFF (not detected, count ¼ 0), as described before (15). In short, we calculated the frequency of expression (OFF/ON analysis), and features expressed four times more frequently in NSCLC were determined as turned ON.…”