Journal Article

67 Integrated spatial multiomics on xenium in situ platform reveals complex heterogeneity in clear cell renal cell carcinoma

Park, Minkyung, Kumar, Vijay, Kravitz, Stephanie, Ikoma Hayato, Espenel Cedric, Ryvkin, Paul, Hensel, Janine, Stauffer Weston, Dadhwal Smritee, Taylor, Sarah, Pham, Kristen, Chang Hsin Wen, Zhang Thanutra, Pathare Suyog, Christopherson Cheyenne, Muñoz, Veronica Gonzalez

2025

نظرة عامة

BackgroundDissecting complex tissue biology at high resolution requires integrated spatial multiomics, yet existing platforms often lack a unified workflow for simultaneous protein and RNA analysis from a single tissue section. We present a novel protein capability for the Xenium In Situ platform that addresses this deficiency, enabling concurrent protein and RNA analysis from the same FFPE tissue within the same, fully integrated, automated workflow. This approach offers unparalleled resolution for characterizing intricate biological processes. Our multiomics solution supports up to 27 immune oncology protein markers and is compatible with Xenium 480-plex gene expression panels across diverse tissue types, providing enhanced resolution for biological investigation.MethodsWe applied our multiomic workflow to simultaneously detect 27 protein and 477 RNA targets in FFPE clear cell renal cell carcinoma (ccRCC) samples. We performed integrated analysis of protein and RNA data to extensively characterize the tumor microenvironment (TME) in ccRCC to interrogate disease state and progression.ResultsThe ccRCC TME comprises diverse immune cell types whose interplay with tumor cells is critical for disease pathogenesis and response to therapy. Our integrated spatial proteomics and transcriptomics approach resulted in enhanced accurate immune cell typing and elucidated critical cell state information by revealing functional phenotypes. Integrative clustering analysis revealed significant spatial and molecular heterogeneity within the ccRCC TME, identifying distinct spatially-organized cellular neighborhoods. We further identified molecular signatures enriched in distinct cell populations and cellular neighborhoods, providing key insights into their biological roles in ccRCC pathogenesis and potential therapeutic vulnerabilities.ConclusionsCompared to studying protein or RNA alone, spatial multiomics, which integrates protein and transcriptomic data together, offers complementary and superior advantages for studying complex tissue biology. We present a robust, fully integrated workflow on the Xenium In Situ platform, enabling simultaneous transcriptomic and proteomic profiling within a tissue sample. Our results highlight the power of this multiomic platform in dissecting the ccRCC TME, revealing complex spatial.

• الناشر: BMJ Publishing Group LTD
• موضوع: Kidney cancer / Pathogenesis / Proteins