PO.TB07.03 · 肿瘤生物学
建立连接妇科肿瘤原代与次级生物样本的多机构整合资源平台
Development of a multi-institutional integrated resource platform linking primary and secondary biospecimens in gynecologic cancers
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摘要 Abstract
中文摘要
背景：
妇科肿瘤表现出显著的分子和组织病理学异质性，凸显了对将高质量生物样本与多组学及功能性资源相整合的基础设施的需求。为满足这一需求，我们建立了一个由七个中心组成的框架，收集标准化的原代生物样本并为妇科肿瘤生成次级资源，并辅以整合的临床和病理数据集。
方法：
原代生物样本——包括血清、血浆、白膜层、尿液、腹水、冷冻肿瘤组织和福尔马林固定石蜡包埋（FFPE）蜡块——根据标准操作规程（SOP）进行采集，分析前变量采用标准分析前编码（SPREC）记录。冷冻组织用于支持高深度全基因组测序（WGS）以及患者来源异种移植（PDX）和类器官模型的建立。FFPE蜡块用于构建组织微阵列（TMA）。人卵巢表面上皮（HOSE）细胞经过标准永生化程序处理以建立稳定细胞系。
结果：
截至2025年11月5日，已入组372例患者（161例子宫内膜癌、101例卵巢癌、104例宫颈癌和6例罕见肿瘤），产生了超过6,000份原代生物样本。在可获得时使用肿瘤-正常配对样本进行WGS，生成了403个数据集：215个肿瘤基因组（60×/90×）和188个正常基因组（30×），代表191例子宫内膜癌、35例卵巢癌和177例宫颈癌病例。构建的TMA包含373个子宫内膜癌、260个宫颈癌、490个卵巢癌组织芯。此外，建立了17个PDX模型（7个子宫内膜癌、8个宫颈癌、2个卵巢癌），以及两个类器官模型和五个IHOSE细胞系。重要的是，原代生物样本、WGS数据集和PDX模型均来自同一批患者，形成了患者匹配的资源，能够在单个患者层面直接整合基因组、病理和功能数据。
结论：
这一多机构平台将标准化的原代生物样本与广泛的次级资源相整合，在妇科肿瘤领域提供了一个罕见的患者关联结构。WGS数据集、TMA、PDX和类器官模型以及IHOSE细胞系的联合可用性支持基因组-病理关联、生物标志物开发以及治疗反应的功能研究。其可扩展的设计为推进妇科肿瘤研究提供了持久的基础设施。
查看英文原文 English abstract
Background:
Gynecologic cancers exhibit substantial molecular and histopathologic heterogeneity, highlighting the need for infrastructures that integrate high-quality biospecimens with multi-omics and functional resources. To address this need, we established a seven-center framework that collects standardized primary biospecimens and generates secondary resources for gynecologic cancers, supported by integrated clinical and pathological datasets.
Methods:
Primary biospecimens-including serum, plasma, buffy coat, urine, ascites, frozen tumor tissues, and formalin-fixed paraffin-embedded (FFPE) blocks-were collected under Standard Operating Procedures (SOPs), with pre-analytical variables recorded using the Standard PRE analytical Code (SPREC). Frozen tissues supported high-depth whole-genome sequencing (WGS) and the development of patient-derived xenograft (PDX) and organoid models. FFPE blocks were used to construct tissue microarrays (TMAs). Human ovarian surface epithelial (HOSE) cells were subjected to standard immortalization procedures to establish stable cell lines.
Results:
As of November 5, 2025, 372 patients (161 endometrial, 101 ovarian, 104 cervical cancers, and 6 rare tumors) had been enrolled, yielding more than 6,000 primary biospecimens. WGS was performed using tumor-normal paired samples when available, generating 403 datasets: 215 tumor genomes (60×/90×) and 188 normal genomes (30×), representing 191 endometrial, 35 ovarian, and 177 cervical cancer cases. TMAs were constructed with 373 endometrial, 260 cervical, 490 ovarian cores. In addition, 17 PDX models were established (7 endometrial, 8 cervical, 2 ovarian), along with two organoid models and five IHOSE cell lines. Importantly, the primary biospecimens, WGS datasets, and PDX models were all generated from the same patients, creating a patient-matched resource that enables direct integration of genomic, pathologic, and functional data at the individual-patient level.
Conclusions:
This multi-institutional platform integrates standardized primary biospecimens with a broad set of secondary resources, providing a rare patient-linked structure in gynecologic cancers. The combined availability of WGS datasets, TMAs, PDX and organoid models, and IHOSE cell lines supports genomic-pathologic correlation, biomarker development, and functional studies of therapeutic response. Its scalable design offers a durable infrastructure for advancing gynecologic cancer research.
利益披露 Disclosure
Y. Kim, None..
J. Kim, None..
H. Shin, None..
Y. Lee, None..
J. Kim, None.