Spatial Multi-omics Reveals the Heterogeneity of Tumor Microenvironment in the OSF-Associated OSCC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220978 | GEO | 2024/03/05
REPOSITORIES: GEO
Similar Datasets
Project description:Oral submucous fibrosis (OSF) as one of the malignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. The role of long non-coding RNA (lncRNA) expression in OSF malignant progression is still poorly understood. Genome-wide lncRNA expression profiling of normal mucous, OSF and OSCC tissues was performed by RNA sequencing. Bioinformatic methods were applied for differential lncRNA analysis and functional enrichment analysis. Quantitative-RT-PCR was used to verify identified lncRNAs.21 novel transcripts were differentially expressed among all three stages during OSF progression with varied expression levels. Our study firstly comprehensively elucidated lncRNAs expression profile of the process of OSCC premalignant lesion to OSCC.
2019-02-13 | GSE125866 | GEO
Project description:In Asia, oral cancer (OC) and oral submucous fibrosis (OSF) constitute major health problems linked to use of betel quid. This work performed CGH genome-wide analysis of OC (12 from India, 12 from Sri Lanka) and OSF (6 from India) cases with normal controls.
2011-11-30 | E-MTAB-819 | biostudies-arrayexpress
Project description:DNA methylation data of normal buccal mucosa and Oral Submucous Fibrosis (OSF) afflicted mucosa.
2021-07-24 | GSE156669 | GEO
Project description:ABSTRACT: Background: Oral Submucous Fibrosis (OSF) is a chronic inflammatory disease resulting in progressive fibrosis of the oral soft tissues. Habit of chewing betel quid has been proposed as an important etiological factor in the development of this disease. But the exact mechanism of pathogenesis is still not clear. Methods: We took microarray approach to identify differentially regulated genes in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results have been confirmed by qRT-PCR. Regulation of genes in epithelial and fibroblast cells was studied after treatment with arecoline, TGF-b and LAP followed by qRT-PCR. Results: Total number of genes found to be commonly regulated in OSF (p<=0.05 and Fold change>=1.5) tissues are 5288 and among them 2884 are up-regulated and 2404 are down-regulated. Extra cellular matrix genes that have been reported in OSF such as collagens, fibronectin and cytokines ET1, CTGF and TGF-b1 are among the up regulated genes. The list of up and down regulated genes also includes RARRES1, TGM2, THBS1, CHGB, MMP3, SPP1 and ALOX12, C4orf7 respectively. Analysis of microarray data revealed TGF-? pathway as a principal gene network involved in the development of OSF. Intriguingly, there was no regulation of CTGF and THBS1 in fibroblasts by arecoline. However, TGF-b1 treatment regulated all these genes in both epithelial and fibroblast cells. Conclusion: We demonstrate over expression of novel genes in OSF and suggest that OSF development involves TGF-b pathway in an epithelial-stromal cooperation. Targeting TGF-b signaling could be an alternate strategy to treat OSF. Two-condition experiment: 10 OSF tissues against 8 pooled normal tissues
2010-07-30 | E-GEOD-20170 | biostudies-arrayexpress
Project description:Objectives. Oral verrucous hyperplasia (OVH) is commonly observed in the oral cavity of betel quid chewers that histologically display epithelial hyperplasia with or without dysplasia. Because of the high frequency of synchronous OVH adjacent to oral carcinomas, OVH is considered a potential malignant disorder, and studies of prognostic factors and genetic alterations are required. Materials and Methods. We conducted a follow-up study of 269 OVH patients at Chi-Mei Medical Center. A Kaplan-Meier analysis and Cox's proportional-hazards regression model were used to calculate the survival rate and prognostic factors of disease recurrence and transformation. Copy number variations (CNVs) were analyzed using a single-nucleotide polymorphism (SNP) array. Results. The 5-year disease-free and cancer-free survival rates of patients with OVH were 52% and 77%, respectively. Heavy betel quid (BQ) chewing (>20 nuts/day), the severity of oral submucosal fibrosis (OSF), and non-buccal and non-tongue lesions were high risk factors for malignant transformation, while dysplasia did not affect outcomes. A genetic analysis showed that OVH already possessed many CNVs present in oral squamous cell carcinoma (OSCC), and a bioinformatics analysis of CNV-associated genes revealed that the upregulation of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 could help identify high-risk OVH patients. Conclusions. BQ-associated OVH has a high malignant potential, and more attention must be paid to OVH patients who have a heavy BQ chewing habit and advanced OSF, and whose tumor is located at non-buccal and non-tongue regions. The five CNV-associated genes can be used for early diagnosis and for predicting the prognosis.
2019-07-01 | GSE101761 | GEO
Project description:Background: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19+MIF+ epithelial cells and via epithelial-stromal crosstalk. Conclusions: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
2024-05-17 | GSE262446 | GEO
Project description:ABSTRACT: Background: Oral Submucous Fibrosis (OSF) is a chronic inflammatory disease resulting in progressive fibrosis of the oral soft tissues. Habit of chewing betel quid has been proposed as an important etiological factor in the development of this disease. But the exact mechanism of pathogenesis is still not clear. Methods: We took microarray approach to identify differentially regulated genes in 10 OSF tissues against 8 pooled normal tissues using oligonucleotide arrays. Microarray results have been confirmed by qRT-PCR. Regulation of genes in epithelial and fibroblast cells was studied after treatment with arecoline, TGF-b and LAP followed by qRT-PCR. Results: Total number of genes found to be commonly regulated in OSF (p<=0.05 and Fold change>=1.5) tissues are 5288 and among them 2884 are up-regulated and 2404 are down-regulated. Extra cellular matrix genes that have been reported in OSF such as collagens, fibronectin and cytokines ET1, CTGF and TGF-b1 are among the up regulated genes. The list of up and down regulated genes also includes RARRES1, TGM2, THBS1, CHGB, MMP3, SPP1 and ALOX12, C4orf7 respectively. Analysis of microarray data revealed TGF-? pathway as a principal gene network involved in the development of OSF. Intriguingly, there was no regulation of CTGF and THBS1 in fibroblasts by arecoline. However, TGF-b1 treatment regulated all these genes in both epithelial and fibroblast cells. Conclusion: We demonstrate over expression of novel genes in OSF and suggest that OSF development involves TGF-b pathway in an epithelial-stromal cooperation. Targeting TGF-b signaling could be an alternate strategy to treat OSF.
2010-06-30 | GSE20170 | GEO
Project description:MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway. Total RNA was obtained from 40 pairs of OSCC patients with tumor specimens and their adjacent non-tumorous epithelia.
2015-01-07 | E-GEOD-45238 | biostudies-arrayexpress
Project description:According to epidemiological studies, a vast majority, approximately 80%~90% of male OSCC patients in Taiwan habitually drink alcohol (A), and chew betel quid (B), and use cigarette (C). To assess the impact of these dietary factors on the epigenome, we conduct a high-throughput screen survey in an oral cancer cohort with exposure of A, B, and C. Results indicate aberrent methylation patterns are prevalent in OSCC patients with ABC risk factors. Genomic DNA was collected from tumor and non-tumor pair-wise samples. These biopsies were obtained from 40 male OSCC patients who regularly drink alcohol, chew areca nut and smoking.
2015-04-01 | E-GEOD-38532 | biostudies-arrayexpress
Project description:According to epidemiological studies, a vast majority, approximately 80%~90% of male OSCC patients in Taiwan habitually drink alcohol (A), and chew betel quid (B), and use cigarette (C). To assess the impact of these dietary factors on the transcriptom, we conduct a high-throughput screen survey in an oral cancer cohort with exposure of A, B, and C. Results indicate several potential oncogenes and tumor suppressor genes are dysregulated in OSCC patients with ABC risk factors. Total RNA was collected from tumor and non-tumor pair-wise samples. These biopsies were obtained from 40 male OSCC patients who regularly drink alcohol, chew areca nut and smoking.
2013-05-02 | E-GEOD-37991 | biostudies-arrayexpress