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. 2025 Aug 11;43(8):1495-1511.e7.
doi: 10.1016/j.ccell.2025.06.004. Epub 2025 Jun 26.

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

Lisa Schweizer  1 , Hilary A Kenny  2 , Rahul Krishnan  2 , Lucy Kelliher  2 , Agnes J Bilecz  2 , Janna Heide  2 , Leonhard Donle  2 , Aasa Shimizu  2 , Andreas Metousis  3 , Rachelle Mendoza  4 , Thierry M Nordmann  3 , Sarah Rauch  2 , Sabrina Richter  5 , Yan Li  6 , Florian A Rosenberger  3 , Maximilian T Strauss  7 , Katherine C Kurnit  2 , Marvin Thielert  3 , Edwin Rodriguez  3 , Johannes B Müller-Reif  3 , S Diane Yamada  2 , Fabian J Theis  5 , Andreas Mund  7 , Ricardo R Lastra  4 , Matthias Mann  8 , Ernst Lengyel  9
Affiliations

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

Lisa Schweizer et al. Cancer Cell. .

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.

Keywords: borderline tumor; deep visual proteomics; low-grade serous cancer; mass spectrometry; metastasis; ovarian cancer; pathology; proteomics; transcriptomics.

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Conflict of interest statement

Declaration of interests E.L. receives research funding to study the biology of ovarian cancer from AbbVie through the University of Chicago, which is unrelated to this work. L.S. is a current employee of OmicVision Biosciences ApS; M.S. and A. Mund are co-founders and shareholders of OmicVision Biosciences ApS. F.J.T. consults for Immunai Inc., Singularity Bio B.V., CytoReason Ltd, Cellarity, and has ownership interest in Dermagnostix GmbH and Cellarity. M.M. is an indirect investor in Evosep and OmicVision Biosciences ApS. The other authors declare no potential conflicts of interest in the context of this manuscript.

Update of

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