Proteogenomic characterisation of Primary Oral Cancer Unveils Extracellular Matrix Remodelling and Immunosuppressive Microenvironment Linked to Lymph Node Metastasis

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2025 Mar 5

PMID 40038875

Authors

Yu Liu

Zhenyu Yang

Jingya Jane Pu

Jie Zhong

Ui-Soon Khoo

Yu-Xiong Su

Gao Zhang

Affiliations

Soon will be listed here.

Abstract

Oral squamous cell carcinoma (OSCC) is an increasingly prevalent malignancy worldwide. This study aims to understand molecular alterations associated with lymph node metastasis of OSCC in order to improve treatment strategies. We analysed a cohort of 46 patients with primary OSCC, including 10 with lymph node metastasis and 36 without. Using a comprehensive multi-omics approach - encompassing genomic, transcriptomic, proteomic, epigenetic, single-cell, and spatial analyses - we integrated data to delineate the molecular landscape of OSCC in the context of lymph node metastasis. Our genomic analysis identified significant mutations in key genes within the MAPK, TGF-β and WNT signalling pathways, which are essential for tumour development. The proteogenomic analysis highlighted pathways critical for lymph node dissemination and factors contributing to an immunosuppressive tumour microenvironment. Elevated levels of POSTN were found to reorganise the extracellular matrix (ECM), interact with TGF-β, disrupt cell cycle regulation and suppress the immune response by reducing VCAM1 activity. Integrated analyses of single-cell and spatial transcriptome data revealed that cancer-associated fibroblasts (CAFs) secrete TGF-β1/2, promoting cancer cell metastasis through epithelial-mesenchymal transition (EMT). Our integrated multi-omics analysis provides a detailed understanding of molecular mechanisms driving lymph node metastasis of OSCC. These insights could lead to more precise diagnostics and targeted treatments. This article is protected by copyright. All rights reserved.

Citing Articles

Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis.

Liu Y, Yang Z, Pu J, Zhong J, Khoo U, Su Y Clin Transl Med. 2025; 15(3):e70261.

PMID: 40038875 PMC: 11879901. DOI: 10.1002/ctm2.70261.

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