Decoding the Dynamic Landscape of Sequential Disease Stages from Oral Submucous Fibrosis to Oral Squamous Cell Carcinoma

Sep 22, 2026

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Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant oral mucosal disorder, yet the mechanism driving its malignant transformation into oral squamous cell carcinoma (OSCC) remains unclear. This study maps spatiotemporal changes in cellular behavior across normal, OSF, margin, and OSCC tissues using 10x Visium spatial transcriptomics combined with single-cell transcriptomic data. Results show fibroblast phenotypic shifts across stages, adaptive immune dominance in OSF and immunosuppression in OSCC. A low-activity intermediate transitional zone and increased tumor-margin cell-cell communication implicate microenvironment reprogramming during invasion, supporting targets for early intervention and prevention.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Study aim

Methods

Key findings

Transitional zone and implications

Scientiﬁc Research Report Decoding the Dynamic Landscape of Sequential Disease Stages from Oral Submucous Fibrosis to Oral Squamous Cell Carcinoma Xin Bin a,b,\#, Jingyi Chenga,b,\#, Jianjun Wu a,b, Zhangui Tang a,b, Yufei Sun c, Kaixin Sua,b, Kun Lia,b, Yanjian Hua,b, Hongzhi Quana,b, Zhiyuan Denga,b, Baisheng Wang a,b, Qian Tang a,b*, Ousheng Liu a,b* a Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, Hunan, China b Hunan Key Laboratory of Oral Health Research & Hunan Clinical Research Center of Oral Major Diseases and Oral Health & Academician Workstation for Oral-maxilofacial and Regenerative Medicine, Central South University, Changsha, Hunan, China c Department of General Surgery, Xiangya Hospital, Central South University, Hunan, China A R T I C L E I N F O Article history: Received 24 December 2025 Received in revised form 4 May 2026 Accepted 6 June 2026 Available online xxx Key words: Oral submucous ﬁbrosis Malignant transformation Cancer invasion Oral squamous cell carcinoma Spatial transcriptomics A B S T R A C T Oral submucous ﬁbrosis (OSF) is a chronic and progressive disease of the oral mucosa that is considered potentially malignant. However, the speciﬁc mechanism of OSF occurrence and malignant transformation into oral squamous cell carcinoma (OSCC) is still unclear. This study aimed to elucidate the spatiotemporal changes in cellular biological behaviour during the occurrence and malignant transformation of OSF, providing new insights for understanding the underlying mechanism and developing novel therapeutic strategies. Sets of normal, OSF, margin area, and OSCC tissue samples were collected, and 10 £ Visium spatial transcriptomics technology was used for sequencing library construction. The spatial transcriptomic data were combined with single-cell transcriptomic data for analysis. Phenotypic shifts in ﬁbroblasts drove the progression of diverse disease stages, and immune cell patterns revealed adaptive immune dominance in OSF and immunosuppression in OSCC. A distinctive transitional zone with low transcriptional activity and intermediate transcriptomic features between noncancerous and cancer cells wasidentiﬁed at the forefront of the cancer invasion margin. Moreover, cancer-side cells had increased cell-cell communication around the tumour margin, reprogramming the adjacent microenvironment to facilitate invasion. The differential end states of epithelial cells demonstrated that basal epithelial cells were the dominant cell source of cancer cells in List of abbreviations: A2M,(Alpha-2-Macroglobulin); CA,(Cancer); CAF,(Cancer-Associated Fibroblast); CA-P, (Peri-cancerous/Margin Area); CCL,(C-C Motif Chemokine Ligand); CD44,(Cluster of Differentiation 44); cDNA,(Complementary DNA); CLDN5,(Claudin 5); CSC,(Cancer Stem Cell); CXCL,(C-X-C Motif Chemokine Ligand); CYP1B1,(Cytochrome P450 Family 1 Subfamily B Member 1); DEG,(Differentially Expressed Gene); ECM,(Extracellular Matrix); EMT,(Epithelial-Mesenchymal Transition); FDR,(False Discovery Rate); GO,(Gene Ontology); GSVA,(Gene Set Variation Analysis); H&E,(Hematoxylin and Eosin); HSPG2,(Heparan Sulfate Proteoglycan 2); IGHG,(Immunoglobulin Heavy Constant Gamma); KEGG,(Kyoto Encyclopedia of Genes and Genomes); KNN,(K-Nearest Neighbors); log2FC,(Log2 Fold Change); MALAT1,(Metastasis Associated Lung Adenocarcinoma Transcript 1); MEG3,(Maternally Expressed 3); MERFISH,(Multiplexed Error-Robust Fluorescence In Situ Hybridization); MFB,(Myoﬁbroblast); MIA,(Multimodal Intersection Analysis); MSigDB,(Molecular Signatures Database); NF,(Normal Fibroblast); NK,(Natural Killer); OCT,(Optimal Cutting Temperature); OPMDs,(Oral Potentially Malignant Disorders); OSCC,(Oral Squamous Cell Carcinoma); OSF,(Oral Submucous Fibrosis); PCA,(Principal Component Analysis); PI3K,(Phosphoinositide 3-kinase); POSTN,(Periostin); PPI,(Protein-Protein Interaction); RARRES2,(Retinoic Acid Receptor Responder

FAQs

What is the main scientific goal of the study?

To elucidate spatiotemporal changes in cellular biological behavior during OSF occurrence and malignant transformation into OSCC, providing mechanistic insights and potential therapeutic directions.

How were tissue samples and sequencing data used in the analysis?

Normal, OSF, margin area, and OSCC tissues were collected, spatial transcriptomics libraries were generated using 10x Visium, and the spatial data were integrated with single-cell transcriptomic data for analysis.

What cellular patterns were observed across OSF and OSCC?

Fibroblast phenotypes shifted with disease progression, while immune-cell patterns indicated adaptive immune dominance in OSF and immunosuppression in OSCC.

Sep 22, 2026

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