超灵敏的检测循环LINE-1 ORF1p作为一种特异性的多癌症生物标记物。
Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker.
发表日期：2023 Sep 12
作者：
Martin S Taylor, Connie Wu, Peter C Fridy, Stephanie J Zhang, Yasmeen Senussi, Justina C Wolters, Tatiana Cajuso, Wen-Chih Cheng, John D Heaps, Bryant D Miller, Kei Mori, Limor Cohen, Hua Jiang, Kelly R Molloy, Brian T Chait, Michael G Goggins, Irun Bhan, Joseph W Franses, Xiaoyu Yang, Mary-Ellen Taplin, Xinan Wang, David C Christiani, Bruce E Johnson, Matthew Meyerson, Ravindra Uppaluri, Ann Marie Egloff, Elyssa N Denault, Laura M Spring, Tian-Li Wang, Ie-Ming Shih, Jennifer E Fairman, Euihye Jung, Kshitij S Arora, Osman H Yilmaz, Sonia Cohen, Tatyana Sharova, Gary Chi, Bryanna L Norden, Yuhui Song, Linda T Nieman, Leontios Pappas, Aparna R Parikh, Matthew R Strickland, Ryan B Corcoran, Tomas Mustelin, George Eng, Omer H Yilmaz, Ursula A Matulonis, Steven J Skates, Bo R Rueda, Ronny Drapkin, Samuel J Klempner, Vikram Deshpande, David T Ting, Michael P Rout, John LaCava, David R Walt, Kathleen H Burns
来源：
Cancer Discovery
摘要：
乳房癌不是一种单一的疾病，而是一组异质的疾病，包括不同的亚型和分子亚型，其病理和生物学特征各不相同。个体患者的免疫状况、基因突变、转录表达谱以及其他因素与患者治疗反应和预后之间的关联仍然不明确。通过理解乳房癌的生物学特征和分子机制，我们可以发现新的乳房癌标志物，并进一步开发更有效的治疗策略，从而提高患者的生存率和生活质量。虽然已经发现了一些乳房癌标志物，如肿瘤标志物CA 15-3和CA 27.29，但它们的敏感性和特异性仍然有待改善，因此需要开发新的生物标志物来更准确地诊断和监测乳房癌。
Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. While proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 M) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multi-analyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multi-cancer biomarker with potential utility for disease detection and monitoring.