Inaugurating High-Throughput Profifiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection

          开创细胞外囊泡的高通量分析用于早期卵巢癌检测

主讲人：刘清源

Advanced Science Pub Date : 2023-07-23 , DOI:10.1002/advs.202301930

Abstract：

    Detecting early cancer through liquid biopsy is challenging due to the lack of specifific 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, specififically 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 fallopiantube (mFT) cells with oncogenic mutations and performs proteomic analyses on mFT-derived EVs. The identifified 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 fifive candidates, EpCAM, CD24, VCAN, HE4, and TNC. The combined expression of these markers distinguishes HGSOC from non-cancer with 89% sensitivity and 93% specifificity. The same markers are also effffective in classifying three groups (non-cancer, early-stage HGSOC, and late-stage HGSOC). The developed approach, for the fifirst 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.

摘要：

由于缺乏早期病变的特异性生物标志物，并且这些标志物的水平可能较低，因此通过液体活检检测早期癌症具有挑战性。目前的研究系统地开发了一种基于细胞外囊泡(EV)的早期检测方法，特别关注高级别浆液性卵巢癌(HGSOC)。标记选择是基于对HGSOC发病机制的新见解，特别是它起源于输卵管内的前体病变。因此，这项工作建立了具有致癌突变的小鼠输卵管(mFT)细胞，并对mFT衍生的ev进行了蛋白质组学分析。然后用原位HGSOC动物模型评估鉴定的标记物。在连续抽取的荷瘤小鼠血液中，mFT-EV标记物随着肿瘤的发生而增加，这支持了它们在早期癌症检测中的潜在应用。一项初步临床研究(n=51)进一步将EV标志物缩小到5个候选标志物，EpCAM、CD24、VCAN、HE4和TNC。这些标记的联合表达将HGSOC与非癌区分开来，灵敏度为89%，特异性为93%。同样的标记也可以有效地分为三组(非癌症、早期HGSOC和晚期HGSOC)。该方法首次应用于输卵管源性EVs，可能成为一种微创工具，用于监测卵巢癌高危妇女，以便及时干预。