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Integration of Multiple Spatial Omics Modalities Reveals Unique Insights into Molecular Heterogeneity of Prostate Cancer

ABSTRACT: This project introduces a spatial multi-omics (SMOx) pipeline integrating MALDI-2 mass spectrometry imaging (MSI) with Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) to investigate molecular heterogeneity in human prostate cancer (PCa). MALDI-2 MSI was used to map lipid distributions with enhanced sensitivity compared to conventional MALDI, enabling detailed visualization of metabolic alterations across tissue regions. Through non-rigid co-registration via H&E images and Gaussian-weighted granularity matching, MSI data were spatially aligned with transcriptomic and histological layers. This integration revealed lipidgene expression relationships associated with distinct cell populations and pathological states within heterogeneous prostate tissues. The resulting dataset provides a high-resolution molecular atlas of PCa, demonstrating the power of MSI-driven spatial multi-omics to uncover lipid-based signatures that refine tissue annotation and support molecular pathology studies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prostate Gland

DISEASE(S): Prostate Cancer

SUBMITTER: Lorenzo Venturelli

LAB HEAD: Johan Swinnen

PROVIDER: PXD070149 | Pride | 2025-10-31

REPOSITORIES: Pride

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			Action	DRS
	929_cancer_new_MSI.h5ad	Other
	929_normal_new_MSI.h5ad	Other
	931_cancer_new_MSI.h5ad	Other
	931_normal_new_MSI.h5ad	Other
	934_cancer_new_MSI.h5ad	Other

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Project description:It has been recognised for a long time that cell surface glycans plays a vital role in the biological process and their altered form can lead to cancer. However, the molecular details and regulatory mechanism between the glycans and cancer is yet not clear. Over the past decade mass spectrometry-based techniques has become a prominent method for analysing glycans especially N-glycan matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). It is a powerful technique that combines mass spectrometry with histology, enabling the visualisation and label free detection of N-linked glycans on a single tissue section. Here, we carried out N-glycan MALDI MSI on six endometrial cancer (EC) formalin fixed paraffin embedded (FFPE) tissue sections including the adjacent normal endometrium, and tissue microarrays (TMA) consisting of 8 EC patients with lymph node metastasis (LNM) and 20 without LNM. By doing that several m/z values were detected that can significantly distinguish normal endometrium from cancerous. Also, detected a m/z value that can discriminate the primary tumour with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose in tumour regions compared to normal with AUC ranges from 0.85-0.99. Whereas, complex N-glycans were detected in lower abundance with AUC ranges from 0.03-0.28. Comparison of N-glycans between the primary tumours with LNM and without LNM indicates reduced abundance of a complex core-fucosylated N-glycan in patients with metastasis relative to without. In summary, N-glycan MALDI MSI can be used to characterize the cancerous endometrium from the normal, also patients with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).

Dataset Information

Integration of Multiple Spatial Omics Modalities Reveals Unique Insights into Molecular Heterogeneity of Prostate Cancer

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