The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer

• Published in: The American journal of pathology Vol. 194; no. 8; pp. 1424 - 1442
• Main Authors: Korsgaard, Ulrik, García-Rodríguez, Juan L., Jakobsen, Theresa, Ahmadov, Ulvi, Dietrich, Kim-Gwendolyn, Vissing, Stine M., Paasch, Thea P., Lindebjerg, Jan, Kjems, Jørgen, Hager, Henrik, Kristensen, Lasse S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2024
• Subjects: Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - metabolism; RNA, Untranslated - genetics; Transcriptome - genetics
• ISSN: 0002-9440; 1525-2191; 1525-2191
• DOI: 10.1016/j.ajpath.2024.04.003

A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body–specific RNAs, pseudogenes, and circular RNAs, as well as RNAs denoted as miscellaneous RNAs, was profiled by total RNA sequencing. In addition to well-known coding and noncoding RNAs, differential expression analysis also uncovered transcripts that have not been implicated previously in colon cancer, such as RNA5SP149, RNU4-2, and SNORD3A. Moreover, there was a profound global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in more advanced tumors. A global down-regulation of circular RNAs in tumors relative to normal tissues was observed, although only a few were expressed differentially between tumor stages. Many previously undescribed transcripts, including RNU6-620P, RNU2-20P, VTRNA1-3, and RNA5SP60, indicated strong prognostic biomarker potential in receiver operating characteristics analyses. In summary, this study unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colon cancer. Notably, there was a significant global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in advanced tumors. Many of these newly discovered candidates demonstrate a strong prognostic potential for stage II colon cancer.