Project description:Array Comparative Genomic Hybridization (CGH) profiling of Oral Leukoplakia (OPL) and early stage Oral Squamous Cell Carcinoma (OSCC) was performed to delineate candidate non-random chromosomal loci associated with disease progression and clinico-pathological parameters. The array CGH hybridizations were performed for 24 OPL and 38 OSCC samples with pooled gender matched controls. All tissue samples were collected after obtaining written informed consent.
Project description:Gene Expression Profiling of Oral Leukoplakia (OPL) and Early Stage Oral Squamous Cell Carcinoma (OSCC) was performed to delineate candidate gene/s clusters with potential to distinguish normal, OPL and tumor tissue from Gingivobuccal complex. All tissue samples were collected after obtaining written informed consent. The RNA profile of 15 OPL and 34 OSCC samples was compared with 1 independent controls Gingivobuccal complex tissue from healthy donors.
Project description:Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide including the Asian subcontinent. Oral carcinoma exhibits inherent heterogeneity in terms of the sites involved, etiology and pathology. They occur at multiple sites such as tongue, buccal mucosa, maxilla. Effective approaches towards improving survival rates in OSCC patients are primarily focused on early detection of the disease. The early clinical indication of the disease follows the development of potentially malignant lesions (leukoplakia/erythro-leukoplakia) with varied rates of transformation. Currently histopathological evaluation of oral biopsy is generally practiced to evaluate potential malignancy. However, human saliva has been considered to be a valuable medium for discovering biomarker molecules for malignancy. Exfoliated cancer cells may release protein or RNA molecules into the saliva or free molecules may be secreted or leaked from cancer cells representing gene expression changes associated with tumor development. Salivary proteins thus provide a strong option for development of non-invasive, point-of-care assays for screening/early detection of oral cancers. Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which is an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, we have used quantitative mass spectrometry to identify differently abundant salivary proteins in OSCC (buccal mucosa) patients and individuals with potential to develop cancer (oral dysplastic leukoplakia) in comparison to healthy controls (with risk habits such as tobacco chewing or smoking).
Project description:Background: Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Methods: Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Results: Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. Conclusions: The three plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.
Project description:Oral leukoplakia (OLK), a recognized oral potentially malignant disorder, demonstrates significant susceptibility to malignant transformation into oral squamous cell carcinoma (OSCC). This study aimed to investigate the involvement of migrasomes, novel intercellular communication organelles, in the carcinogenesis of OLK. Migrasomes were observed through electron microscopy and multiplex immunofluorescence in OLK and OSCC tissues, and the purified migrasomes were characterized by wheat germ agglutinin staining, long-term imaging, Western blot, and electron microscopy. Single-cell RNA sequencing analysis was conducted to evaluate the effect of migrasomes on the microenvironment. The combined analysis of the quantitative proteome of migrasomes and the transcriptome of recipient cells was used to investigate the involvement of migrasomes in the carcinogenesis of OLK. Xenograft tumors and a mouse model of tongue leukoplakia helped verify migrasomes’ participation in carcinogenesis. Migrasomes were found in both human OLK and OSCC tissues. Notably, migrasomes isolated from dysplastic oral keratinocyte DOK cells, DOK-transformed cells, and OSCC cell lines exhibited characteristic morphological features and distinct molecular signatures. A significant correlation existed between migrasome score and the infiltration of immune cells. Moreover, the protein cargoes within migrasomes promoted leukoplakia carcinogenesis by inducing an immunosuppressive microenvironment. This study reveals that migrasomes drive leukoplakia carcinogenesis. It not only deepens the understanding of the interaction between dysplastic keratinocytes and immune cells during this process but also provides potential diagnostic biomarkers or targets for the treatment of the precancer stage of OSCC.
Project description:Genome-wide expression array measurements for 9 head and neck squamous cell carcinomas (HNSCC) stratified by worst pattern of invasion (WPOI) Jayakar et al. (2016). Apolipoprotein E promotes invasion in oral squamous cell carcinoma. Li et al. (2013). Validation of the risk model: high-risk classification and tumor pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma.
Project description:Microarray was used to find out the differentially expressed in tumor sites of early-stage oral squamous cell carcinoma compared with Normal parts. Furthermore, we compared cases of early-stage oral squamous cell carcinoma with lymph node metastasis with cases without lymph node metastasis. The miRNAs obtained may not only serve as predictive biomarkers for lymph node metastasis, but may also be used further to understand disease.