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

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

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

Language: Английский

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Downregulation of SMAD2 and SMAD4 is associated with poor prognosis and shorter survival in esophageal squamous cell carcinoma

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 3, 2025

Language: Английский

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Fibrosis‐Encapsulated Tumoroid, A Solid Cancer Assembloid Model for Cancer Research and Drug Screening

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Abstract Peritumoral fibrosis is known to promote cancer progression and confer treatment resistance in various solid tumors. Consequently, developing accurate research drug screening models that replicate the structure function of a fibrosis‐surrounded tumor mass imperative. Previous studies have shown self‐assembly three‐dimensional (3D) co‐cultures primarily produce cancer‐encapsulated or maintain fibrosis‐encapsulated for short period, which inadequate fibrosis, particularly as physical barrier. To address this limitation, multi‐layer spheroid formation method developed create tumoroid (FET) maintains structural stability up 14 days. FETs exhibited faster growth, higher expression immunosuppressive cytokines, equal greater anticancer drugs compared their parental tumoroids. Additionally, serve versatile model traditional research, enabling study exosomal miRNA gene functions, well mechanobiology when combined with alginate hydrogel. Our findings suggest FET represents an advanced more accurately mimics tissue peritumoral fibrosis. It may show potential superiority over self‐assembly‐based 3D screening, holds promise personalized selection treatment.

Language: Английский

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Integrin Targeting and Beyond: Enhancing Cancer Treatment with Dual-Targeting RGD (Arginine–Glycine–Aspartate) Strategies

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1556 - 1556

Published: Nov. 20, 2024

Integrins, an important superfamily of cell adhesion receptors, play essential role in cancer progression, metastasis, and angiogenesis, establishing them as prime targets for both diagnostic therapeutic applications. Despite their significant potential, integrin-targeted therapies have faced substantial challenges clinical trials, including variable efficacy unmet high expectations. Nevertheless, the consistent expression integrins on tumor stromal cells underscores ongoing relevance potential. Traditional RGD-based imaging agents limitations, such inconsistent target rapid systemic clearance, which reduced effectiveness. To overcome these challenges, recent research has focused advancing strategies exploring innovative solutions. This review offers a thorough analysis latest developments RGD–integrin field, with particular focus addressing previous limitations. It delves into new dual-targeting approaches cutting-edge designed to improve diagnosis outcomes. By examining advancements, this illuminates pathways enhancing specificity therapies, paving way more effective treatment strategies.

Language: Английский

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BBOX1‐AS1 promotes gastric cardia adenocarcinoma progression via interaction with CtBP2 to facilitate the epithelial–mesenchymal transition process

Cancer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Abstract It is recognized that lncRNA BBOX1‐AS1 exerts a crucial oncogenic property in several cancer types. However, the functions and underlying mechanisms of epithelial–mesenchymal transition (EMT) process gastric cardia adenocarcinoma (GCA) have remained unclarified. The findings this study demonstrated GCA tissues had elevated expression levels, which was associated with worse prognosis patients. dramatically enhanced cell proliferation, invasion, TGF‐β1‐induced EMT vitro. Further mechanism analysis revealed could combine CtBP2 strengthen interaction ZEB1. might regulate E‐cadherin through CtBP2/ZEB1 transcriptional complex‐mediated repression, further affecting activation Wnt/β‐catenin pathway process. Overall, our demonstrate act as an for facilitating advancement via to facilitate process, indicated it function exploitable treatment target

Language: Английский

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