Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Antioxid Redox Signal. 2022 Jan;36(1-3):39-56. doi: 10.1089/ars.2020.8244. Epub 2021 Dec 21.
Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAF mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs . We aim to identify the target of this peptide. Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. binding assays and immunofluorescence staining of human colon specimens supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAF mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAF mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress and can serve as an imaging biomarker for detection of SSAs. . 36, 39-56.
无柄锯齿状腺瘤(SSA)是由 BRAF 突变驱动的癌前病变,导致结直肠癌(CRC)的发生。由于其外观细微,在白光结肠镜检查中经常被遗漏。此前,已证明荧光标记的 7 肽 KCCFPAQ 可用于检测 SSA。我们旨在确定该肽的靶标。过氧化物酶 1(Prdx1)被鉴定为该肽配体的结合伴侣。与人类结肠标本的结合测定和免疫荧光染色支持了这一结果。具有 BRAF 突变的细胞的膜上过表达 Prdx1,并且这种作用依赖于氧化应激。携带 BRAF 突变的 RKO 细胞和人类 SSA 标本显示出更高的氧化应激以及细胞膜上 Prdx1 的水平升高。这些结果表明,在氧化应激存在的情况下,Prdx1 在细胞表面过度表达,可作为检测 SSA 的成像生物标志物。。36, 39-56。