Shenoy, U Sangeetha, Morgan, Richard, Hunter, Keith 
ORCID: 0000-0002-7873-0877, Kabekkodu, Shama Prasada and Radhakrishnan, Raghu
(2022)
Integrated computational analysis reveals HOX genes cluster as oncogenic drivers in head and neck squamous cell carcinoma.
SCIENTIFIC REPORTS, 12 (1).
7952-.
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Integrated computational analysis reveals HOX genes cluster as oncogenic drivers in head and neck squamous cell carcinoma.pdf - Published version Download (4MB) | Preview |
Abstract
Alterations in homeobox (HOX) gene expression are involved in the progression of several cancer types including head and neck squamous cell carcinoma (HNSCC). However, regulation of the entire HOX cluster in the pathophysiology of HNSCC is still elusive. By using different comprehensive databases, we have identified the significance of differentially expressed HOX genes (DEHGs) in stage stratification and HPV status in the cancer genome atlas (TCGA)-HNSCC datasets. The genetic and epigenetic alterations, druggable genes, their associated functional pathways and their possible association with cancer hallmarks were identified. We have performed extensive analysis to identify the target genes of DEHGs driving HNSCC. The differentially expressed HOX cluster-embedded microRNAs (DEHMs) in HNSCC and their association with HOX-target genes were evaluated to construct a regulatory network of the HOX cluster in HNSCC. Our analysis identified sixteen DEHGs in HNSCC and determined their importance in stage stratification and HPV infection. We found a total of 55 HNSCC driver genes that were identified as targets of DEHGs. The involvement of DEHGs and their targets in cancer-associated signaling mechanisms have confirmed their role in pathophysiology. Further, we found that their oncogenic nature could be targeted by using the novel and approved anti-neoplastic drugs in HNSCC. Construction of the regulatory network depicted the interaction between DEHGs, DEHMs and their targets genes in HNSCC. Hence, aberrantly expressed HOX cluster genes function in a coordinated manner to drive HNSCC. It could provide a broad perspective to carry out the experimental investigation, to understand the underlying oncogenic mechanism and allow the discovery of new clinical biomarkers for HNSCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Head and Neck Neoplasms, Prognosis, Gene Expression Regulation, Neoplastic, Genes, Homeobox, Carcinogenesis, Biomarkers, Tumor, Squamous Cell Carcinoma of Head and Neck |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Oct 2022 14:01 |
| Last Modified: | 05 May 2023 10:55 |
| DOI: | 10.1038/s41598-022-11590-1 |
| Open Access URL: | https://www.nature.com/articles/s41598-022-11590-1 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165608 |
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