Exploring the microbiome of oral epithelial dysplasia as a predictor of malignant progression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816925 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18338900_1.fastq.gz | Fastqsanger.gz | |||
| SRR18338900_2.fastq.gz | Fastqsanger.gz | |||
| SRR18338901_1.fastq.gz | Fastqsanger.gz | |||
| SRR18338901_2.fastq.gz | Fastqsanger.gz | |||
| SRR18338902_1.fastq.gz | Fastqsanger.gz |
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Project description:A growing body of research associates the oral microbiome and oral cancer. Well-characterized clinical samples with outcome data are required to establish relevant associations between the microbiota and disease. The objective of this study was to characterize the community variations and the functional implications of the microbiome in low-grade oral epithelial dysplasia (OED) using 16S rRNA gene sequencing from annotated archival swabs in progressing (P) and non-progressing (NP) OED. We characterised the microbial community in 90 OED samples - 30 swabs from low-grade OED that progressed to cancer (cases) and 60 swabs from low-grade OED that did not progress after a minimum of 5 years of follow up (matched control subjects). There were small but significant differences between P and NP samples in terms of alpha diversity as well as beta diversity in conjunction with other clinical factors such as age and smoking status for both taxa and functional predictions. Across all samples, the most abundant genus was Streptococcus, followed by Haemophilus, Rothia, and Neisseria. Taxa and predicted functions were identified that were significantly differentially abundant with progression status (all Ps and NPs), when samples were grouped broadly by the number of years between sampling and progression or in specific time to progression for Ps only. However, these differentially abundant features were typically present only at low abundances. For example, Campylobacter was present in slightly higher abundance in Ps (1.72%) than NPs (1.41%) and this difference was significant when Ps were grouped by time to progression. Furthermore, several of the significantly differentially abundant functions were linked to the Campylobacteraceae family in Ps and may justify further investigation. Larger cohort studies to further explore the microbiome as a potential biomarker of risk in OED are warranted.
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Project description:Oral malignancies are among the top most deadly cancers in the world. Early diagnosis of oral premalignant and malignant lesions is essential for treatment decision-making and prognosis improvement. In this study, we systematically evaluated the gene expression patterns during the pathogenesis of oral moderate dysplasia. RNA sequencing detected 21556 genes in moderate dysplasia and paired normal tissues from three patients. Hierarchical clustering analysis revealed distinct gene expression patterns between the moderate dysplasia samples. 346 differentially expressed genes that may contribute to the pathogenesis of moderate dysplasia were identified. Among these genes, ISG15 and MAGEA family showed different transcription profiles that close related with the alterations of gene expression patterns in moderate dysplasia samples and paired normal tissues. We speculated that, as the potential marker to signal the risk of malignant transformation, ISG15 and MAGEA together with their close related misexpressed genes may involve in two different pathways during the malignant conversion from oral dysplasia to oral squamous cell carcinoma.
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Project description:Breast malignant phyllodes tumors (PTs) are rapid-progressing tumors, known to lack effective treatment and suitable prognostic markers as well as elaborate studies. Herein,we found that level of CD146 is progressively elevated with malignant progression of PTs and is an independent predictor for prognosis of PT patients.Mechanistically, CD146 activates the PI3K/AKT signaling pathway, thereby enhancing malignant behaviors of PT cells.This study unveils a CD146-PI3K/AKT axis in modulating the malignant progression of PTs, and open avenues to develop a novel target for precise prognosis and treatment for breast malignant PTs.
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Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. Oral carcinogenesis is a multifactorial process involving numerous genetic changes that affect the activity of oncogenes, tumor suppressor genes and other classes of disease-related genes.Therefore, to identify the responsive genes for progression of oral dysplasia or OSCC, we here performed CGH analysis to DNA from oral dysplasia and OSCC by microdissection Copy number analysis of Affymetrix 250K SNP arrays was performed for 8 oral dysplasia samples, 8 oral squamous cell carcinoma samples, using microdissection
2013-10-22 | E-GEOD-51265 | biostudies-arrayexpress
Project description:The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of genetic alterations. Oral carcinogenesis is a multifactorial process involving numerous genetic changes that affect the activity of oncogenes, tumor suppressor genes and other classes of disease-related genes.Therefore, to identify the responsive genes for progression of oral dysplasia or OSCC, we here performed CGH analysis to DNA from oral dysplasia and OSCC by microdissection
2013-10-22 | GSE51265 | GEO
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.
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Project description:Understanding the dynamics of the immune microenvironment is critical to the development of immuno-prevention strategies for the prevention of oral potentially malignant disorders transformation to oral squamous cell carcinoma (OSCC). We generated gene expression profiles of the microdissected epithelial and stromal compartments normal mucosa, hyperplasia, dysplasia and invasive tumors in the 4-nitroquinolein (4-NQO) murine model of oral carcinogenesis. Most gene expression changes were observed in the stromal compartment and related to immune biological processes. Immune cell deconvolution identified infiltration by the macrophage population as the most important quantitatively especially at the stage of dysplasia. In 86 patients with oral leukoplakia, three M2 macrophages signatures were independently associated and highly predictive of improved oral cancer-free survival.
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Project description:The aim of the study was to address the concept of field cancerization in oral cancer. The presence of genomic aberrations, indicative of chromosomal instability (CIN), in oral distant fields (ODFs) of visually normal and non-dysplastic mucosa at the mirror image from concomitant oral potentially malignant lesions (OPMLs) was investigated. This pilot study comprised 16 OPMLs (8 without dysplasia, nd-OPMLs; 8 with dysplasia, d-OPMLs) and 16 ODFs. DNA diploid (DNA Index, DI=1) and aneuploid (DIM-bM-^IM- 1) sublines were detected by high resolution DNA-flow cytometry (FCM) at (hr DNA-FCM) using DAPI stained nuclei suspensions. Nuclei with different DIs were FCM-sorted in order to enrich the epithelial component and to obtain genomic DNA for high resolution oligonucleotide array-Comparative Genomic Hybridization (a-CGH) analysis to provide a genome-wide measurement of DNA copy number aberrations (CNAs). The frequencies of DNA aneuploidy in ODFs and OPMLs were 6.2% and 43.8%, respectively (p=0.037). ODFs and nd-OPMLs were all near-diploid (DIM-bM-^IM- 1 and DIM-bM-^IM-$1.4), while d-OPMLs were also high-aneuploid (DI>1.4). CNA averages were 2.3 in ODFs (1.5 for nd-OPMLs and 3.1 for d-OPMLs), and 7.325 in OPMLs (3.0 in nd-OPMLs; 11.6 in d-OPMLs). CNAs were present in the DNA diploid sublines and often the same CNAs were observed in both ODFs and corresponding OPMLs DNA aneuploid sublines and CNAs in the present series of 16 ODFs are likely to represent early events of the natural history of oral carcinogenesis and to indicate an early onset of the field effect cancerization. Moreover, gains within 20q13.33-qter, 7p22.2-pter and 16p13.3-pter chromosomal regions in ODFs and in the relative OPMLs suggest that specific genes localized in these regions (RTEL1, MAD1L1 and TEL2) might contribute to the ODF/d-OPML transition. We analyzed: 8 samples of oral potentially malignant lesions with dysplasia, 8 samples of oral potentially malignant lesions without dysplasia and for each patient a corresponding oral distant field of visually normal mucosa.
2011-12-21 | E-GEOD-28906 | biostudies-arrayexpress
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