近日，美国芝加哥大学教授Ernst Lengyel及其研究小组探明了空间蛋白质转录组学分析揭示了交界性卵巢肿瘤及其侵袭性进展的分子景观。这一研究成果于2025年6月26日发表在国际顶尖学术期刊《癌细胞》上。

研究人员整合了细胞类型分解的空间蛋白质组学和转录组学来阐明从SBT到LGSC的进化及其在基质和肿瘤中的相应转移。这种转变通过具有微乳头状特征的中间阶段发生在上皮间室内，在此期间，LGSC过表达c-Met和几种脑特异性蛋白。在肿瘤微环境中，癌细胞和基质细胞之间的相互联系，以及降解堆积的细胞外基质的酶，表明各种细胞类型之间存在功能协作。课题组研究人员通过整合空间转录组学和蛋白质组学对16个药物靶点进行了功能验证。靶向CDK4/6 （milciclib）和FOLR1 （mirvetuximab）的联合治疗在体内实现了显著的肿瘤减少，代表了一种有前景的LGSC治疗策略。

研究人员表示，上皮性血清交界性肿瘤（SBT）是一种非侵袭性卵巢肿瘤，可复发为耐药低级别血清癌（LGSC）。虽然遗传改变表明有一个共同的起源，但从SBT到LGSC的转变仍然知之甚少。

附：英文原文

Title: Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression

Author: Lisa Schweizer, Hilary A. Kenny, Rahul Krishnan, Lucy Kelliher, Agnes J. Bilecz, Janna Heide, Leonhard Donle, Aasa Shimizu, Andreas Metousis, Rachelle Mendoza, Thierry M. Nordmann, Sarah Rauch, Sabrina Richter, Yan Li, Florian A. Rosenberger, Maximilian T. Strauss, Katherine C. Kurnit, Marvin Thielert, Edwin Rodriguez, Johannes B. Müller-Reif, S. Diane Yamada, Fabian J. Theis, Andreas Mund, Ricardo R. Lastra, Matthias Mann, Ernst Lengyel

Issue&Volume: 2025-06-26

Abstract: Epithelial serous borderline tumors (SBT) are non-invasive neoplastic ovarian lesions that may recur as chemo-resistant low-grade serous cancer (LGSC). While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood. Here, we integrate cell-type resolved spatial proteomics and transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastases in both stroma and tumor. The transition occurs within the epithelial compartment through an intermediary stage with micropapillary features, during which LGSC overexpresses c-Met and several brain-specific proteins. Within the tumor microenvironment, interconnectivity between cancer and stromal cells, along with enzymes degrading a packed extracellular matrix, suggests functional collaboration among various cell types. We functionally validated 16 drug targets identified through integrated spatial transcriptomics and proteomics. Combined treatment targeting CDK4/6 (milciclib) and FOLR1 (mirvetuximab) achieved significant tumor reduction in vivo, representing a promising therapeutic strategy for LGSC.

DOI: 10.1016/j.ccell.2025.06.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00253-3