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Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.
Taylor, Martin S; Wu, Connie; Fridy, Peter C; Zhang, Stephanie J; Senussi, Yasmeen; Wolters, Justina C; Cajuso, Tatiana; Cheng, Wen-Chih; Heaps, John D; Miller, Bryant D; Mori, Kei; Cohen, Limor; Jiang, Hua; Molloy, Kelly R; Chait, Brian T; Goggins, Michael G; Bhan, Irun; Franses, Joseph W; Yang, Xiaoyu; Taplin, Mary-Ellen; Wang, Xinan; Christiani, David C; Johnson, Bruce E; Meyerson, Matthew; Uppaluri, Ravindra; Egloff, Ann Marie; Denault, Elyssa N; Spring, Laura M; Wang, Tian-Li; Shih, Ie-Ming; Fairman, Jennifer E; Jung, Euihye; Arora, Kshitij S; Yilmaz, Osman H; Cohen, Sonia; Sharova, Tatyana; Chi, Gary; Norden, Bryanna L; Song, Yuhui; Nieman, Linda T; Pappas, Leontios; Parikh, Aparna R; Strickland, Matthew R; Corcoran, Ryan B; Mustelin, Tomas; Eng, George; Yilmaz, Ömer H; Matulonis, Ursula A; Chan, Andrew T; Skates, Steven J.
Afiliação
  • Taylor MS; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Wu C; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Fridy PC; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Zhang SJ; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.
  • Senussi Y; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Wolters JC; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Cajuso T; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Cheng WC; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Heaps JD; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Miller BD; Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Mori K; Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Cohen L; Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Jiang H; Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Molloy KR; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Chait BT; Healthcare Optics Research Laboratory, Canon U.S.A., Inc., Cambridge, Massachusetts.
  • Goggins MG; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Bhan I; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
  • Franses JW; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
  • Yang X; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.
  • Taplin ME; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York.
  • Wang X; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York.
  • Christiani DC; Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Johnson BE; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Meyerson M; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Uppaluri R; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Egloff AM; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Denault EN; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Spring LM; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Wang TL; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Shih IM; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Fairman JE; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
  • Jung E; Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Arora KS; Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Yilmaz OH; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Cohen S; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Sharova T; Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Chi G; Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Norden BL; Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Song Y; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
  • Nieman LT; Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.
  • Pappas L; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
  • Parikh AR; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Strickland MR; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Corcoran RB; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Mustelin T; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Eng G; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Yilmaz ÖH; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Matulonis UA; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Chan AT; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Skates SJ; Mass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer Discov ; 13(12): 2532-2547, 2023 12 12.
Article em En | MEDLINE | ID: mdl-37698949
ABSTRACT
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.

SIGNIFICANCE:

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinoma Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Female / Humans Idioma: En Revista: Cancer Discov Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Carcinoma Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Female / Humans Idioma: En Revista: Cancer Discov Ano de publicação: 2023 Tipo de documento: Article