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差异表达 microRNAs 作为溃疡性结肠炎肿瘤进展的新型生物标志物。

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis.

机构信息

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

出版信息

Clin Transl Gastroenterol. 2022 Jul 1;13(7):e00489. doi: 10.14309/ctg.0000000000000489. Epub 2022 Apr 8.

DOI:10.14309/ctg.0000000000000489
PMID:35404333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10476842/
Abstract

INTRODUCTION

Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied.

METHODS

In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs).

RESULTS

Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05).

DISCUSSION

UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.

摘要

简介

结直肠癌（CRC）是长期溃疡性结肠炎（UC）的潜在危及生命的并发症。MicroRNAs（miRNA）是表观遗传调节剂，它们参与了 UC 相关 CRC 的发展。然而，它们作为潜在的黏膜肿瘤进展的生物标志物的作用尚未得到充分研究。

方法

在这项研究中，我们使用 Custom TaqMan Array Cards 分析了 52 例活检（20 例正常黏膜、20 例发育不良和 12 例 UC 相关 CRC）和 50 例对照活检（10 例正常黏膜、21 例散发性腺瘤和 19 例散发性 CRC）中 96 个预选 miRNA 的表达。为了验证下调 miRNA 的准确性，我们在一个独立的 50 例病例队列（13 例正常黏膜、25 例发育不良和 12 例 UC 相关 CRC）和 46 例对照中进行了单独的定量实时聚合酶链反应（19 例散发性腺瘤和 20 例散发性 CRC）。

结果

在 UC 相关 CRC 序列中发现 64 个 miRNA 存在差异下调。选择其中 8 个 miRNA 进行进一步验证。我们证实 miR-31、-106a 和 -135b 在正常黏膜与发育不良之间以及在 UC 相关 CRC 序列中显著下调（均 P <0.01）。值得注意的是，与散发性 CRC 相比，这些 miRNA 也证实具有显著的差异表达（均 P <0.05）。

讨论

UC 相关和散发性 CRC 具有不同的 miRNA 表达模式，一些 miRNA 表明早期肿瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/887d0da0f172/ct9-13-e00489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/c719805dbf24/ct9-13-e00489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/3bda06081d9e/ct9-13-e00489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/3369b364ec6d/ct9-13-e00489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/1614ecb86ca2/ct9-13-e00489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/887d0da0f172/ct9-13-e00489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/c719805dbf24/ct9-13-e00489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/3bda06081d9e/ct9-13-e00489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/3369b364ec6d/ct9-13-e00489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/1614ecb86ca2/ct9-13-e00489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129f/10476842/887d0da0f172/ct9-13-e00489-g005.jpg

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