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环状转录本在结直肠癌中的过表达预示复发及总体生存率低。

Overexpression of Circular Transcripts in Colorectal Adenocarcinoma Predicts Recurrence and Poor Overall Survival.

作者信息

Kokoropoulos Panagiotis, Christodoulou Spyridon, Tsiakanikas Panagiotis, Vassiliu Panteleimon, Kontos Christos K, Arkadopoulos Nikolaos

机构信息

Fourth Department of Surgery, University General Hospital "Attikon", National and Kapodistrian University of Athens, 12462 Athens, Greece.

Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece.

出版信息

Int J Mol Sci. 2025 Jul 11;26(14):6683. doi: 10.3390/ijms26146683.

DOI:10.3390/ijms26146683
PMID:40724932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12294339/
Abstract

Colorectal cancer (CRC) is one of the most prevalent and deadly neoplasms globally; this fact puts emphasis on the need for accurate molecular biomarkers for early detection and accurate prognosis. Circular RNAs (circRNAs) have recently emerged as very promising cancer biomarkers. In this study, we thoroughly examined whether the expression levels of circular transcripts of the protein arginine methyltransferase 1 () gene can predict the prognosis of patients diagnosed with colorectal adenocarcinoma, the most frequent type of CRC. Hence, a highly sensitive quantitative PCR (qPCR) assay was developed and applied to quantify circ-PRMT1 expression in cDNAs from 210 primary colorectal adenocarcinoma tissue specimens and 86 paired normal colorectal mucosae. Extensive biostatistical analysis was then performed to assess the potential prognostic power of circ-PRMT1. Significant overexpression of this molecule was observed in colorectal adenocarcinoma tissue samples in contrast to their non-cancerous counterparts. Moreover, higher circ-PRMT1 expression was correlated with poorer disease-free survival (DFS) and worse overall survival (OS) in colorectal adenocarcinoma patients. Interestingly, multivariate Cox regression analysis revealed that the prognostic value of the expression of this circRNA does not depend on other established prognostic factors included in the prognostic model. Furthermore, the stratification of patients based on TNM staging revealed that higher circ-PRMT1 levels were significantly related to shorter DFS and OS intervals, particularly in patients with colorectal adenocarcinoma of TNM stage II or III. In summary, this original research study provides evidence that circ-PRMT1 overexpression represents a promising molecular biomarker of poor prognosis in colorectal adenocarcinoma, not depending on other established prognostic factors such as TNM staging.

摘要

结直肠癌(CRC)是全球最常见且致命的肿瘤之一;这一事实凸显了对用于早期检测和准确预后的精确分子生物标志物的需求。环状RNA(circRNAs)最近已成为非常有前景的癌症生物标志物。在本研究中,我们全面研究了蛋白质精氨酸甲基转移酶1()基因的环状转录本的表达水平是否能够预测被诊断为结直肠腺癌(CRC最常见的类型)患者的预后。因此,开发了一种高灵敏度定量PCR(qPCR)检测方法,并将其应用于定量210份原发性结直肠腺癌组织标本和86份配对的正常结直肠黏膜cDNA中的circ-PRMT1表达。随后进行了广泛的生物统计学分析,以评估circ-PRMT1的潜在预后能力。与非癌对应组织相比,在结直肠腺癌组织样本中观察到该分子显著过表达。此外,在结直肠腺癌患者中,较高的circ-PRMT1表达与较差的无病生存期(DFS)和总生存期(OS)相关。有趣的是,多变量Cox回归分析显示,这种circRNA表达的预后价值并不取决于预后模型中包含的其他既定预后因素。此外,根据TNM分期对患者进行分层显示,较高的circ-PRMT1水平与较短的DFS和OS间隔显著相关,特别是在TNM II期或III期的结直肠腺癌患者中。总之,这项原创性研究提供了证据,表明circ-PRMT1过表达代表了结直肠腺癌预后不良的一种有前景的分子生物标志物,不依赖于其他既定的预后因素,如TNM分期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e47/12294339/6457e76aca0e/ijms-26-06683-g006.jpg
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本文引用的文献

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Discovery of circular transcripts of the human BCL2-like 12 (BCL2L12) apoptosis-related gene, using targeted nanopore sequencing, provides new insights into circular RNA biology.利用靶向纳米孔测序技术发现人类凋亡相关基因BCL2样12(BCL2L12)的环状转录本,为环状RNA生物学提供了新见解。
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