Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
Cancer Discov. 2023 Dec 12;13(12):2532-2547. doi: 10.1158/2159-8290.CD-23-0313.
Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although 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 mol/L) 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 multianalyte 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 multicancer biomarker with potential utility for disease detection and monitoring.
The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 μL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489.
需要改进的生物标志物用于早期癌症检测、风险分层、治疗选择和监测治疗反应。虽然蛋白质可以作为有用的基于血液的生物标志物，但许多蛋白质在这些应用中具有有限的灵敏度或特异性。长散布元件-1（LINE-1）开放阅读框 1 蛋白（ORF1p）是一种转座元件蛋白，在癌变过程中在癌和高危前体中过度表达，在正常组织中表达可忽略不计，这表明 ORF1p 可能是一种高度特异性的癌症生物标志物。为了探索 ORF1p 作为基于血液的生物标志物，我们设计了超灵敏的数字免疫测定法，该方法可在多种癌症中检测到血浆中具有高特异性的中原子摩尔（10-17 mol/L）浓度的 ORF1p。血浆 ORF1p 有望用于早期检测卵巢癌，在多分析物组中提高诊断性能，在胃食管癌中提供早期治疗反应监测，并在胃食管和结直肠癌中具有总体生存预后。总之，这些观察结果将 ORF1p 作为一种多癌生物标志物，具有用于疾病检测和监测的潜在效用。
LINE-1 ORF1p 转座子蛋白在许多癌症中普遍表达，是组织和血液中多种常见致命性癌及其高危前体的高度特异性生物标志物。从少至 25 μL 血浆中获得的超灵敏 ORF1p 测定是癌症检测和监测的新型、快速、具有成本效益的工具。请参阅 Doucet 和 Cristofari 的相关评论，第 2502 页。本文选自本期重点文章，第 2489 页。
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