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Data from Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas

Version 2 2024-10-30, 14:40
Version 1 2024-08-01, 07:26
Posted on 2024-10-30 - 14:40
AbstractPurpose:

The landscape of extracellular matrix (ECM) alterations in soft tissue sarcomas (STS) remains poorly characterized. We aimed to investigate the tumor ECM and adhesion signaling networks present in STS and their clinical implications.

Experimental Design:

Proteomic and clinical data from 321 patients across 11 histological subtypes were analyzed to define ECM and integrin adhesion networks. Subgroup analysis was performed in leiomyosarcomas (LMS), dedifferentiated liposarcomas (DDLPS), and undifferentiated pleomorphic sarcomas (UPS).

Results:

This analysis defined subtype-specific ECM profiles including enrichment of basement membrane proteins in LMS and ECM proteases in UPS. Across the cohort, we identified three distinct coregulated ECM networks which are associated with tumor malignancy grade and histological subtype. Comparative analysis of LMS cell line and patient proteomic data identified the lymphocyte cytosolic protein 1 cytoskeletal protein as a prognostic factor in LMS. Characterization of ECM network events in DDLPS revealed three subtypes with distinct oncogenic signaling pathways and survival outcomes. Evaluation of the DDLPS subtype with the poorest prognosis nominates ECM remodeling proteins as candidate antistromal therapeutic targets. Finally, we define a proteoglycan signature that is an independent prognostic factor for overall survival in DDLPS and UPS.

Conclusions:

STS comprise heterogeneous ECM signaling networks and matrix-specific features that have utility for risk stratification and therapy selection, which could in future guide precision medicine in these rare cancers.

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FUNDING

Sarcoma UK (SUK)

Cancer Research UK (CRUK)

NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research (BRC)

Royal Marsden Cancer Charity (The Royal Marsden Cancer Charity)

Institute of Cancer Research (ICR)

German Research Foundation

German Federal Ministry of Education

Sarcoma Foundation of America (SFA)

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AUTHORS (19)

Valeriya Pankova
Lukas Krasny
William Kerrison
Yuen B. Tam
Madhumeeta Chadha
Jessica Burns
Christopher P. Wilding
Liang Chen
Avirup Chowdhury
Emma Perkins
Alexander T.J. Lee
Louise Howell
Nafia Guljar
Karen Sisley
Cyril Fisher
Priya Chudasama
Khin Thway
Robin L. Jones
Paul H. Huang
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