Early changes in the immune microenvironment during oral tumorigenesis reveal an unexpected protective role of M2 macrophages in oral potentially malignant disorders
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ABSTRACT:
PROVIDER: PRJNA691354 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13407001_1.fastq.gz | Fastqsanger.gz | |||
| SRR13407001_2.fastq.gz | Fastqsanger.gz | |||
| SRR13407002_1.fastq.gz | Fastqsanger.gz | |||
| SRR13407002_2.fastq.gz | Fastqsanger.gz | |||
| SRR13407003_1.fastq.gz | Fastqsanger.gz |
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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.
2022-01-11 | GSE164619 | GEO
Project description:A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed ‘non-transforming’ (NT) cases. Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected p-value was < 0.05. RNA yield was variable but RNA purity was good (A260/A280 >1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases. Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the aetiopathogenesis of OPMD and development of novel biomarkers.
2020-08-14 | GSE156208 | GEO
Project description:Gene expression changes associated with malignant transformation of oral potentially malignant disorders
| PRJNA657049 | ENA
Project description:Oral potentially malignant disorders (OPMDs) may precede oral squamous cell carcinoma (OSCC). Early detection of OPMDs has a crucial role in OSCC prevention. DNA aneuploidy and chromosomal aberrations are markers of genomic DNA damage and chromosomal instability (CIN), which is involved in cancer development. We explored the relationship among genomic DNA copy number aberrations (CNAs), histological diagnosis and DNA aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed for high resolution DNA flow cytometry (hr DNA-FCM) to determine the relative DNA content expressed with the DNA index (DI). Additionally, on a subset of these samples, array-Comparative Genomic Hybridization (aCGH) analysis was performed on DNA obtained from diploid nuclei suspension or from aneuploid-enriched nuclei suspensions. DNA copy number aberrations were determined using high resolution arrays on 151 samples (2x105K, n=82 samples, and 4x180K, n=69 samples) (Agilent Technologies, Palo Alto, CA, USA). Labeling, hybridization, scanning and feature extraction were performed as previously described using the cross hybridization method previously described [Castagnola P, Malacarne D, Scaruffi P, Maffei M, Donadini A, et al. (2011) Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue. BMC Cancer 11: 445.].
2015-10-23 | E-GEOD-66136 | biostudies-arrayexpress
Project description:The mucosae of the oral cavity are different at the histological level but are all exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. We analyzed: 19 samples (4 aneuploid and 15 diploid components) deriving from oral potentially malignant lesions without dysplasia obtained of 16 patients; 14 samples (2 aneuploid and 12 diploid components) deriving from oral potentially malignant lesions with dysplasia obtained from 11 patients (two patients had multiple dysplastic lesions); 2 samples from visually normal mucosa in the near field obtained from two patients with dysplastic lesions. All the aneuploid samples had a purity of at least 90%.
2011-10-19 | E-GEOD-28868 | biostudies-arrayexpress
Project description:Oral potentially malignant disorders (OPMDs) may precede oral squamous cell carcinoma (OSCC). Early detection of OPMDs has a crucial role in OSCC prevention. DNA aneuploidy and chromosomal aberrations are markers of genomic DNA damage and chromosomal instability (CIN), which is involved in cancer development. We explored the relationship among genomic DNA copy number aberrations (CNAs), histological diagnosis and DNA aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed for high resolution DNA flow cytometry (hr DNA-FCM) to determine the relative DNA content expressed with the DNA index (DI). Additionally, on a subset of these samples, array-Comparative Genomic Hybridization (aCGH) analysis was performed on DNA obtained from diploid nuclei suspension or from aneuploid-enriched nuclei suspensions.
2015-10-23 | GSE66136 | GEO
Project description:ObjectivesDentists play a major role in the diagnosis of oral potentially malignant disorders (OPMDs) that may lead to malignancy. Their knowledge on OPMDs and the risk factors associated with malignant disease needs to be sufficient. The aim of this study was to assess the level of knowledge, attitudes, and awareness of OPMDs amongst general dentists and dental specialists working in Saudi Arabia.Material and methodsQuestionnaires were distributed to dentists working in Saudi Arabia. A total of 303 dentists participated in the study. The questionnaire included 20 questions on knowledge, attitudes, and awareness of OPMDs.ResultsThe response rate was 55%. There was no significant difference between general dental practitioners and dental specialists regarding leukoplakia, which is the most common OPMD (P > .05) and in identifying tobacco and alcohol as the main risk factors for malignant transformation of OPMDs into cancer (P > .05). However, there was a significant difference (P < .05) between specialists (75.3%) and general practitioners (52.3%) in the diagnosis of OPMDs. There was a significant difference (P < .05) between specialists (63.5%) and general practitioners (28.0%) in recognising the likelihood of malignant transformation of proliferative verrucous leukoplakia. There was a significant difference between specialists (61.2%) and general practitioners (25.2%, P < .05) in recognising the erosive form or atrophic type of oral lichen planus, considering that it is more likely to undergo malignant transformation.ConclusionsDental specialists have better knowledge and awareness than general dentists regarding OPMDs. Improved continuous education programmes on the risk factors and diagnosis of OPMDs should be organised to train dentists.
| S-EPMC9275301 | biostudies-literature
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
Project description:The mucosae of the oral cavity are different at the histological level but are all exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study.
2011-10-20 | GSE28868 | GEO
Project description:The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.
| S-EPMC7072384 | biostudies-literature