이학호 (기초과학연구원, Massachusetts General Hospital Research Institute, Harvard Medical School) | 한빛사논문 > 한빛사

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기초과학연구원, Massachusetts General Hospital Research Institute, Harvard Medical School

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Adv. Sci., 2023 Jul 23;e2301930 | https://doi.org/10.1002/advs.202301930 Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection

Ala Jo ^{1 2 3}, Allen Green ⁴, Jamie E Medina ⁴, Sonia Iyer ⁵, Anders W Ohman ⁴, Eric T McCarthy ⁴, Ferenc Reinhardt ⁵, Thomas Gerton ⁴, Daniel Demehin ⁴, Ranjan Mishra ⁵, David L Kolin ⁴, Hui Zheng ⁶, Jinwoo Cheon ³, Christopher P Crum ⁴, Robert A Weinberg ⁵, Bo R Rueda ⁷, Cesar M Castro ^{1 8 *}, Daniela M Dinulescu ^{4 *}, Hakho Lee ^{1 2 3 *}

¹Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
²Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
³Center for Nanomedicine, Institute for Basic Science, Seoul, 03722, Republic of Korea.
⁴Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
⁵Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
⁶Biostatistics Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁷Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁸Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

^*Corresponding author: correspondence to Cesar M Castro, Daniela M Dinulescu or Hakho Lee

Abstract

Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. The current study systematically develops an extracellular-vesicle (EV)-based test for early detection, specifically focusing on high-grade serous ovarian carcinoma (HGSOC). The marker selection is based on emerging insights into HGSOC pathogenesis, notably that it arises from precursor lesions within the fallopian tube. This work thus establishes murine fallopian tube (mFT) cells with oncogenic mutations and performs proteomic analyses on mFT-derived EVs. The identified markers are then evaluated with an orthotopic HGSOC animal model. In serially-drawn blood of tumor-bearing mice, mFT-EV markers increase with tumor initiation, supporting their potential use in early cancer detection. A pilot clinical study (n = 51) further narrows EV markers to five candidates, EpCAM, CD24, VCAN, HE4, and TNC. The combined expression of these markers distinguishes HGSOC from non-cancer with 89% sensitivity and 93% specificity. The same markers are also effective in classifying three groups (non-cancer, early-stage HGSOC, and late-stage HGSOC). The developed approach, for the first time inaugurated in fallopian tube-derived EVs, could be a minimally invasive tool to monitor women at high risk of ovarian cancer for timely intervention.

논문정보

형식Research article
게재일2023년 07월 (BRIC 등록일 2023-08-22)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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