BCAT1, IKZF1 and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas

被引:3
作者
Laven-Law, Geraldine [1 ,4 ]
Kichenadasse, Ganessan [1 ,2 ]
Young, Graeme P. [1 ]
Symonds, Erin L. [1 ,3 ]
Winter, Jean M. [1 ]
机构
[1] Flinders Univ S Australia, Flinders Hlth & Med Res Inst, Coll Med & Publ Hlth, Adelaide, SA, Australia
[2] Southern Adelaide Local Hlth Network, Flinders Med Ctr, Dept Med Oncol, Adelaide, SA, Australia
[3] Southern Adelaide Local Hlth Network, Flinders Med Ctr, Dept Gastroenterol & Hepatol, Adelaide, SA, Australia
[4] Flinders Ctr innovat Canc, Flinders Dr, Bedford Pk, SA 5043, Australia
关键词
Colorectal cancer; circulating tumour DNA; diagnostic biomarkers; DNA methylation; oesophageal cancer; gastric cancer; COLORECTAL-CANCER; VALIDATION;
D O I
10.1080/1354750X.2024.2340663
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Introduction: Methylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1 (COLVERA) and SEPT9 (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1 and SEPT9 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 BCAT1, IKZF1 and SEPT9 methylation, and the selectivity of hypermethylated BCAT1, IKZF1 and SEPT9 for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression. Results: Hypermethylated BCAT1, IKZF1 and SEPT9 were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1 was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1 and SEPT9 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 BCAT1/IKZF1 and SEPT9 might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.
引用
收藏
页码:194 / 204
页数:11
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