Analysis of differentially expressed genes in dysplastic oral keratinocyte cell line and their role in the development of HNSCC.

Dysplasia is the presence of abnormal types of cells in a tissue precipitated by over or diminished expression of certain genes. These cells act as a precursor to cancer. Dysplastic oral keratinocyte (DOK) cell lines have an aneuploid complex karyotype. They provide an opportunity to study the action of specific carcinogens on malignant transformations. This study aimed to identify the differentially expressed genes in dysplastic cells and their possible association with head and neck squamous cell carcinoma (HNSCC). These genes can be developed as diagnostic, prognostic, or therapeutic leads.The list of genes related to oral keratinocyte dysplasia and head and neck cancer was accessed from the GEO (Gene Expression Omnibus) database. Gene expression profiling was done between dysplastic oral keratinocytes and normal human oral keratinocytes. Gene expression and Kaplan Meier survival analysis were performed using the UALCAN database to assess the correlations between dysregulated genes identified in dysplastic keratinocytes and primary tumors of HNSCC. The GEO omnibus dataset identified numerous differentially expressed genes of which the top 10 up and downregulated genes in dysplastic oral keratinocytes were curated for further analysis. The expression profile of these genes was assessed using the HNSCC dataset (TCGA, Firehose Legacy). Among all the genes assessed, only one gene, the OLR1 gene encoding oxidized low-density lipoprotein, was found to be overexpressed in both the groups viz., dysplastic keratinocytes and HNSCC cases with a strong correlation with the survival status of patients. There was significant correlation between the gene expression pattern observed in dysplastic keratinocytes and the primary tumor of the HNSCC group, with an exotic gene that was seldom discussed in association with cancer, viz., OLR1. Exploration into other top-ranking differentially expressed genes in dysplastic cases would aid in identifying the candidate gene associated with both phenotypes.

Alteration of SERPINH1 is associated with elevated expression in head and neck squamous cell carcinomas and its clinicopathological significance.

BACKGROUND/PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer-related death worldwide and contributes significantly to the burden of disease in South Asia, partially due to the lack of effective screening strategies. Identifying essential biomarkers is crucial for improved prognosis and treatment. This study investigates the potential of SERPINH1 as a prognostic marker in HNSCC, highlighting its significance amidst the molecular complexity. METHODS: The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumors and 44 normal tissues, was analyzed using cBioportal, UALCAN, and Protein atlas tools. Expression patterns, survival outcomes, and clinical correlations of SERPINH1 were evaluated. In-depth analyses involved oral squamous cell carcinoma (OSCC) patient samples, protein expression, and functional exploration using various in-silico tools. RESULTS: SERPINH1 exhibited significant alteration and upregulation in HNSCC and OSCC, indicating its pan-cancer potential. Immunohistochemistry confirmed its overexpression in primary HNSCC tumors. Association analyses linked altered SERPINH1 levels with tumor stage, grade, metastasis, human papillomavirus (HPV) status, and patient prognosis. Functional analyses unveiled SERPINH1's involvement in critical cellular pathways and interactions with various proteins. CONCLUSION: The significant alteration of SERPINH1 associated with upregulated expression in HNSCC and OSCC positions it as a promising diagnostic and prognostic marker. Further investigations are warranted to elucidate the underlying molecular mechanisms, paving the way for targeted therapeutic interventions and continued exploration of various malignancies.

Deciphering the Genetic Alteration in the ZEB2 Gene Network and Their Possible Association With Head and Neck Squamous Cell Carcinoma (HNSCC).

Background Head and neck squamous cell carcinoma (HNSCC) is an abnormal growth of cells that leads to tumor formation in the head and neck region. Several genes and genetic networks are involved in the process of carcinogenesis. Aim The aim of the present study is to unravel the prognostic marker from a pool of interacting networks governed by the ZEB2gene. Materials and methods Computational analysis was employed to identify the protein network interactions, genetic alterations, gene expression, and the survival analysis of the ZEB2 dysregulated network in the head and neck cancer dataset (HNSCC) from the Cancer Genome Atlas (TCGA), Firehose Legacy. The gene expression profiling and survival analysis were performed for the gene with the highest frequency of genetic alteration. Result The interaction network returned nine genes that interact with ZEB2. The ARHGAP31 gene was found to harbor the highest frequency of alteration at the genomic as well as the transcriptomic levels. Survival was also found to be significant with respect to the differential gene expression pattern while comparing the genders and different ethnic groups. Females with higher expression of ARHGAP31 and the Asian population exhibiting low/medium expression of the same were found to present with poor survival probability. Conclusion The identification of putative drivers or a candidate gene of a network could provide clues about the association with the disease phenotype of HNSCC. The present study identifies ARHGAP31 as the key gene of the ZEB2 gene network, wherein the genetic alterations correlate with the transcriptomics data and the survival probability of patients segregated based on gender and race. Further experimental evaluation is warranted to confirm the association of this infamous gene ARHGAP31 with the development of oral carcinoma.