Biology subjects

Szylberg, L.

Publications and source records attributed to Szylberg, L..

2 recordsLinked to original sources

bioRxiv2026

Spatial Transcriptomics of TNBC tumours and corresponding lymph node metastasis reveals immune hubs driven by TNF/NF-κB signalling of TMSB4X and CD74 expressing cells.

PurposeLymph node metastasis is a critical prognostic factor in triple-negative breast cancer (TNBC), but the spatial organization of signalling networks driving metastatic colonization and persistence remains poorly defined. Understanding these networks may reveal therapeutic vulnerabilities in metastatic TNBC. MethodsWe applied Visium spatial transcriptomics to paired primary tumours and lymph node metastases from four TNBC patients. Spatial gene expression profiles were analysed using trajectory inference, cell-type deconvolution, and cell-cell communication mapping. Results were validated in independent single-cell RNA sequencing datasets from TNBC tumours and lymph node metastases. ResultsTMSB4X and CD74 emerged as key drivers of metastasis-associated transcriptional programs, defining spatially distinct immune communication hubs enriched in myeloid, stromal, and endothelial cells. These hubs preferentially activated NF-{kappa}B/TNF signalling alongside PI3K-Akt and Rap1 pathways. In primary tumours, NF-{kappa}B/TNF signalling was confined to localized immune hubs, whereas lymph node metastases exhibited widespread signalling across cellular compartments with additional IL-1 pathway activation. This spatial rewiring coincided with endothelial cells assuming central coordinating roles in metastatic lesions. Independent validation confirmed myeloid-endothelial crosstalk as a conserved feature of TNBC, with TMSB4X-CD74 programs enriched in clinically relevant immune and vascular subpopulations. ConclusionTNBC lymph node metastases display spatially expanded inflammatory networks centred on TMSB4X-CD74 immune hubs. Metastatic progression involves coordinated myeloid-endothelial signalling, suggesting these pathways as potential biomarkers and therapeutic targets. Disrupting inflammatory and vascular communication networks may offer a strategy to prevent metastatic persistence and overcome therapy resistance in TNBC.

molecular biology↗

bioRxiv2024

Prelude to Malignancy: A Gene Expression Signature in Normal Mammary Gland from Breast Cancer Patients Suggests Pre-tumorous Alterations and Is Associated with Adverse Outcomes

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes is still missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

genomics↗