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用于检测全胃肠道腺癌的甲基化 DNA 生物标志物。

, and : methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

机构信息

Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Adelaide, South Australia.

Department of Medical Oncology, Flinders Medical Centre, Southern Adelaide Local Health Network, Adelaide, South Australia.

出版信息

Biomarkers. 2024 Jun;29(4):194-204. doi: 10.1080/1354750X.2024.2340663. Epub 2024 Apr 22.

DOI:10.1080/1354750X.2024.2340663
PMID:38644767
Abstract

INTRODUCTION

Methylated circulating tumour DNA (ctDNA) blood tests for (COLVERA) and (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize and methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection.

METHODS

Tissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of and methylation, and the selectivity of hypermethylated , and for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression.

RESULTS

Hypermethylated and were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers , and were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types.

DISCUSSION

Existing CRC methylated ctDNA blood tests for and might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.

摘要

简介

用于检测结直肠癌(CRC)的甲基化循环肿瘤 DNA(ctDNA)血液检测(COLVERA 和 Epi proColon)。然而,目前尚无用于其他胃肠道腺癌的 ctDNA 检测方法。我们旨在研究不同胃肠道腺癌和非胃肠道肿瘤中的 和 甲基化,以确定这些经过验证的 CRC 生物标志物是否可用于泛胃肠道腺癌的检测。

方法

使用癌症基因组图谱中结直肠(COAD、READ)、胃食管(ESCA、STAD)、胰腺(PAAD)和胆管癌(CHOL)腺癌队列的组织 DNA 甲基化数据进行差异甲基化分析。使用贝叶斯回归分别探讨了 和 甲基化的临床病理预测因子,以及与其他癌症相比,高甲基化 的选择性。

结果

和 均在结直肠和胃食管腺癌中存在差异甲基化。 在胰腺腺癌中存在差异甲基化。DNA 生物标志物 、 和 在不同疾病阶段相对稳定,与其他癌症类型相比,对胃肠道腺癌具有高度选择性。

讨论

现有的 CRC 甲基化 ctDNA 血液检测(COLVERA 和 Epi proColon)可能可用于其他胃肠道腺癌,并值得进一步进行前瞻性 ctDNA 研究。

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