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解析微小RNA图谱:探索局部复发性直肠癌的分子动力学

Unraveling the MicroRNA tapestry: exploring the molecular dynamics of locoregional recurrent rectal cancer.

作者信息

Meyer N Helge, Kotnik Nika, Noubissi Nzeteu Gaetan Aime, van Kempen Léon C, Mastik Mirjam, Bockhorn Maximilian, Troja Achim

机构信息

Department of Human Medicine, School of Medicine and Health Sciences, Klinikum Oldenburg, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, Germany.

Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.

出版信息

Front Oncol. 2024 Jul 12;14:1407217. doi: 10.3389/fonc.2024.1407217. eCollection 2024.

Abstract

INTRODUCTION

Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally, with a concerning rise in incidence among young adults. Despite progress in understanding genetic predispositions and lifestyle risk factors, the intricate molecular mechanisms of CRC demand exploration. MicroRNAs (miRNAs) emerge as key regulators of gene expression and their deregulation in tumor cells play pivotal roles in cancer progression.

METHODS

NanoString's nCounter technology was utilized to measure the expression of 827 cancer-related miRNAs in tumor tissue and adjacent non-involved normal colon tissue from five patients with locoregional CRC progression. These expression profiles were then compared to those from the primary colon adenocarcinoma (COAD) cohort in The Cancer Genome Atlas (TCGA).

RESULTS AND DISCUSSION

Intriguingly, 156 miRNAs showed a contrasting dysregulation pattern in reccurent tumor compared to their expression in the TCGA COAD cohort. This observation implies dynamic alterations in miRNA expression patterns throughout disease progression. Our exploratory study contributes to understanding the regulatory landscape of recurrent CRC, emphasizing the role of miRNAs in disease relapse. Notable findings include the prominence of let-7 miRNA family, dysregulation of key target genes, and dynamic changes in miRNA expression patterns during progression. Univariate Cox proportional hazard models highlighted miRNAs associated with adverse outcomes and potential protective factors. The study underscores the need for more extensive investigations into miRNA dynamics during tumor progression and the value of stage specific biomarkers for prognosis.

摘要

引言

结直肠癌(CRC)是全球第三大常见恶性肿瘤,且在年轻人中的发病率呈令人担忧的上升趋势。尽管在了解遗传易感性和生活方式风险因素方面取得了进展,但CRC复杂的分子机制仍有待探索。微小RNA(miRNA)是基因表达的关键调节因子,其在肿瘤细胞中的失调在癌症进展中起关键作用。

方法

利用NanoString的nCounter技术测量了5例局部区域CRC进展患者的肿瘤组织和相邻未受累正常结肠组织中827种癌症相关miRNA的表达。然后将这些表达谱与癌症基因组图谱(TCGA)中原发性结肠腺癌(COAD)队列的表达谱进行比较。

结果与讨论

有趣的是,与它们在TCGA COAD队列中的表达相比,156种miRNA在复发性肿瘤中表现出相反的失调模式。这一观察结果意味着在疾病进展过程中miRNA表达模式的动态变化。我们的探索性研究有助于理解复发性CRC的调控格局,强调了miRNA在疾病复发中的作用。显著发现包括let-7 miRNA家族的突出地位、关键靶基因的失调以及进展过程中miRNA表达模式的动态变化。单变量Cox比例风险模型突出了与不良结局相关的miRNA和潜在的保护因素。该研究强调了在肿瘤进展过程中对miRNA动态进行更广泛研究的必要性以及阶段特异性生物标志物对预后的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8daf/11272531/827e3a711b57/fonc-14-1407217-g001.jpg

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