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

IF 4.7 2区 医学 Q1 PATHOLOGY American Journal of Pathology Pub Date : 2024-08-01 DOI:10.1016/j.ajpath.2024.04.003
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Abstract

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.

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复发性和非复发性结肠癌中编码和非编码 RNA 的转录情况。
相当多的局部或局部晚期结肠癌患者会复发,因此迫切需要更好的预后生物标志物。在这里,我们通过总RNA测序分析了信使RNA(mRNA)、长非编码RNA(lncRNA)、小核RNA(snRNA)、小核仁RNA(snoRNA)、小卡贾尔体特异性RNA(scaRNA)、假基因和环状RNA(circRNA)以及被称为杂项RNA的RNA的转录组图谱。除了众所周知的编码和非编码 RNA 外,差异表达分析还发现了以前从未与结肠癌有关的转录本,如 RNA5SP149、RNU4-2 和 SNORD3A。此外,在较晚期的肿瘤中,snRNA 伪基因、snoRNA 和 rRNA 伪基因出现了显著的整体上调。与正常组织相比,肿瘤中的 circRNAs 出现了全面的下调,而在不同肿瘤分期中,只有极少数的 circRNAs 有差异表达。在 ROC 分析中,包括 RNU6-620P、RNU2-20P、VTRNA1-3 和 RNA5SP60 在内的许多以前未描述过的转录本都显示出很强的预后生物标志物潜力。总之,本研究揭示了复发性和非复发性结肠癌中不同类别的大量差异表达 RNA。值得注意的是,在晚期肿瘤中,snRNA假基因、snoRNA和rRNA假基因出现了显著的整体上调。在这些新发现的候选基因中,有许多都显示出对 II 期结肠癌有很强的预后潜力。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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