PO.CL01.08 · 临床研究

OvaPrint与多组学分析用于附件肿块精确分类的前瞻性验证

Prospective verification of OvaPrint and multi-omic profiling for precise adnexal mass classification

编号 2589 展板 8 时间 4/20 09:00–12:00 区域 Section 46 主讲 Thomas Simon, PhD

分会场 Liquid Biopsies: Circulating Nucleic Acids 2

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Thomas Simon¹, Lynda D. Roman², X. Mona Guo², Ben Yi Tew¹, Gerald C. Gooden¹, Monica Neuman³, Emma Barber⁴, Elisa Romeo⁵, Todd Holscher⁵, Renee Wunderley⁶, Danielle Goldberg⁷, Krishna Morampudi⁷, Dalia Daujotyte⁷, Monique Spillman⁸, Bodour Salhia¹

¹Department of Cancer Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA,²Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA,³Los Angeles General Medical Center, Los Angeles, CA,⁴Division of Gynecologic Oncology, Feinberg School of Medicine, Northwestern University, Evanston, IL,⁵CpG Diagnostics, Inc., Pasadena, CA,⁶Cpg Diagnostics, Inc., Pasadena, CA,⁷Illumina, Inc., San Diego, CA,⁸Department of Gynecologic Oncology, University of Arkansas Medical Center, Little Rock, AR

摘要 Abstract

中文摘要

背景：附件肿块患者既面临过度治疗（当良性疾病被误分类时），也面临治疗不足（当癌症未由妇科肿瘤学家管理时）。CA125是应用最广泛的生物标志物，但缺乏特异度。高级别浆液性卵巢癌（HGSOC）是上皮性卵巢癌（EOC）中最具侵袭性的亚型，需要及时的专科管理。OvaPrint是一种为改善附件肿块评估而开发的cfDNA甲基化液体活检，目前针对HGSOC进行了优化，并正在扩展中。在一项前瞻性多中心研究中，我们旨在对OvaPrint进行临床验证，将其与CA125比较，并将其与5碱基测序、下一代蛋白质组学和空间转录组学分析相整合。方法：术前从美国六个中心采集血浆并用OvaPrint分析。入选标准包括影像学显示附件肿块、无转移性疾病证据且计划手术。临床数据（包括CA125值）从病历中提取。手术病理报告的诊断作为临床金标准。在121例病例（7例HGSOC，16例其他EOC，5例其他癌症，93例良性）中，110例可评估（104例有CA125）。终点为灵敏度、特异度、阳性预测值（PPV）和阴性预测值（NPV）。样本还使用Illumina的最新技术进行分析，包括：检测9500种蛋白质的Illumina蛋白质制备（IPP）平台（80份血浆样本）；用于同时进行全基因组DNA甲基化和变异检测的5碱基测序方案（58份cfDNA样本）；用于描述肿瘤微环境（TME）和组织学背景的空间转录组学（23份新鲜冷冻组织样本）。结果：OvaPrint对HGSOC实现了83.3%的灵敏度。对良性病例的特异度为96.6%，对非HGSOC肿瘤为97.1%。HGSOC特异性的PPV和NPV分别为62.5%和99%。CA125对HGSOC显示100%灵敏度，但特异度差（62.2%，PPV 13%）。IPP、5碱基测序和空间转录组学数据正在评估中，以通过整合的多组学方法补充OvaPrint，用于区分恶性和良性附件肿块。结论：迫切需要用于EOC诊断的准确工具。这项前瞻性多中心研究证明了OvaPrint在辨别HGSOC方面的卓越性能。OvaPrint高的HGSOC特异性NPV和PPV意味着阳性结果几乎可确定为HGSOC，支持及时和适当的诊疗。OvaPrint正在扩展到其他EOC，并正在进行CLIA验证。整合其他分子终点可进一步增强对附件肿块的区分能力。这些发现确立了它作为首个用于HGSOC的液体活检，具有变革诊断实践和预后的潜力。

查看英文原文 English abstract

Background: Patients with adnexal masses face both overtreatment, when benign disease is misclassified, and undertreatment, when cancers are not managed by gynecologic oncologists. CA125, the most widely used biomarker, lacks specificity. High-grade serous ovarian cancer (HGSOC), the most aggressive subtype of epithelial ovarian cancer (EOC), requires timely specialist management. OvaPrint, a cfDNA methylation liquid biopsy developed to improve adnexal mass evaluation, is currently optimized for HGSOC, with expansion underway. In a prospective multi-site study, we sought to clinically verify OvaPrint, compare it with CA125 and integrate it with 5-base sequencing, next generation proteomics and spatial transcriptomics analysis. Methods: Plasma was collected from six US sites preoperatively and analyzed with OvaPrint. Eligibility included adnexal mass on imaging without evidence of metastatic disease and planned surgery. Clinical data, including CA125 values, were abstracted from medical records. Diagnosis from surgical pathology reports served as the clinical ground truth. Of 121 cases (7 HGSOC, 16 other EOCs, 5 other cancers, 93 benign), 110 were evaluable (104 had CA125). Endpoints were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Samples were also analyzed using the latest Illumina's technology including: Illumina's Protein Preparation (IPP) platform detecting 9500 proteins (80 plasma samples); 5-base sequencing solution for simultaneous whole-genome DNA methylation and variant detection (58 cfDNA samples); spatial transcriptomics for description of the tumor microenvironment (TME) and histologic context (23 fresh frozen tissue samples). Results: OvaPrint achieved 83.3% sensitivity for HGSOC. Specificity was 96.6% for benign cases and 97.1% for non-HGSOC tumors. The HGSOC-specific PPV and NPV was 62.5% and 99%, respectively. CA125 showed 100% sensitivity for HGSOC but had poor specificity (62.2%, 13% PPV). IPP, 5-base sequencing and spatial transcriptomics data are being evaluated to complement OvaPrint through an integrated multi-omic approach for the discrimination of malignant and benign adnexal masses. Conclusions: Accurate tools for EOC diagnosis are urgently needed. This prospective, multi-site study demonstrates OvaPrint's exceptional performance for the discernment of HGSOC. The high HGSOC-specific NPV and PPV of OvaPrint means a positive result is a near-certain indicator of HGSOC, supporting timely and appropriate care. OvaPrint is being expanded to other EOCs and is undergoing CLIA validation. Additional integration of other molecular endpoints could further enhance discrimination of adnexal masses. These findings establish it as the first liquid biopsy for HGSOC with potential to transform diagnostic practice and outcomes.

利益披露 Disclosure

T. Simon, None.. L. D. Roman, None.. X. Guo, None.. B. Tew, None.. G. C. Gooden, None.. M. Neuman, None.. E. Barber, None. E. Romeo, CpG Diagnostics, Inc. Employment. T. Holscher, Cpg Diagnostics, Inc. Employment. R. Wunderley, CpG Diagnostics, Inc. Employment. D. Goldberg, Illumina, Inc. Employment. K. Morampudi, Illumina, Inc. Employment. D. Daujotyte, Illumina, Inc. Employment. M. Spillman, None. B. Salhia, CpG Diagnostics, Inc. Other, Founder, Shareholder, Advisor. Illumina, Inc. Other, Advisor.

← 返回 AACR 2026 检索