The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment
Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally, with high morbidity and mortality due to late-stage diagnoses, treatment resistance, and recurrence. Hydrogen sulfide (H2S) metabolism, primarily regulated by cystathionine gamma-lyase (CTH) a...
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SpringerOpen
2025-04-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-025-00715-6 |
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| author | Mohamed Rizwan Ghouse Santhakumar Egambaram Arunkumar Ramachandran Rajesh Parsanathan |
| author_facet | Mohamed Rizwan Ghouse Santhakumar Egambaram Arunkumar Ramachandran Rajesh Parsanathan |
| author_sort | Mohamed Rizwan Ghouse |
| collection | DOAJ |
| description | Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally, with high morbidity and mortality due to late-stage diagnoses, treatment resistance, and recurrence. Hydrogen sulfide (H2S) metabolism, primarily regulated by cystathionine gamma-lyase (CTH) and cystathionine beta-synthase (CBS), plays a crucial role in cancer biology by promoting tumour proliferation and survival. This study investigates the expression and methylation patterns of H2S regulatory genes [CTH, CBS, catalase (CAT), D-amino acid oxidase (DAO), mercaptopyruvate sulfurtransferase (MPST), and sulfide quinone reductase-like protein (SQRDL)] in HNSCC, aiming to understand their role in cancer progression and prognosis. Materials and methods Gene expression and promoter methylation data were analysed using GEPIA2 and UALCAN. Kaplan–Meier survival analysis assessed prognostic relevance. Functional enrichment and protein–protein interaction (PPI) networks were examined using ShinyGO, STRING, and GeneMANIA. Single-cell RNA sequencing from the TISCH2 database provided insights into tumour microenvironment (TME) dynamics. Results CTH, CBS, and SQRDL were significantly upregulated in HNSCC tissues, while DAO remained unchanged. Promoter methylation analysis revealed hypomethylation of CTH and SQRDL, suggesting increased expression, while CBS, MPST, and DAO showed hypermethylation, indicating repression. Kaplan–Meier analysis linked high CTH and CAT expression and low DAO expression to poor overall survival. Functional enrichment highlighted roles in cysteine biosynthesis, sulfur metabolism, and oxidative stress. PPI networks interacted with tumour-related proteins, implicating H2S genes in tumour progression. Single-cell RNA sequencing confirmed differential expression across TME cell types, indicating a role in immune modulation. Conclusion H2S regulatory genes play a significant role in HNSCC progression through altered expression and epigenetic regulation. Their association with patient survival and involvement in critical metabolic pathways, suggest potential as prognostic biomarkers and therapeutic targets. Further clinical validation is needed to explore their utility in personalised HNSCC treatment. |
| format | Article |
| id | doaj-art-9a85ba9a2466435d9e843c624cd7b2cc |
| institution | OA Journals |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-9a85ba9a2466435d9e843c624cd7b2cc2025-08-20T02:20:01ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-04-0126111610.1186/s43042-025-00715-6The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironmentMohamed Rizwan Ghouse0Santhakumar Egambaram1Arunkumar Ramachandran2Rajesh Parsanathan3Department of Biotechnology, School of Integrative Biology, Central University of Tamil NaduDepartment of Biotechnology, School of Integrative Biology, Central University of Tamil NaduMultidisciplinary Research Unit (A Unit of DHR-ICMR), Madras Medical CollegeDepartment of Biotechnology, School of Integrative Biology, Central University of Tamil NaduAbstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally, with high morbidity and mortality due to late-stage diagnoses, treatment resistance, and recurrence. Hydrogen sulfide (H2S) metabolism, primarily regulated by cystathionine gamma-lyase (CTH) and cystathionine beta-synthase (CBS), plays a crucial role in cancer biology by promoting tumour proliferation and survival. This study investigates the expression and methylation patterns of H2S regulatory genes [CTH, CBS, catalase (CAT), D-amino acid oxidase (DAO), mercaptopyruvate sulfurtransferase (MPST), and sulfide quinone reductase-like protein (SQRDL)] in HNSCC, aiming to understand their role in cancer progression and prognosis. Materials and methods Gene expression and promoter methylation data were analysed using GEPIA2 and UALCAN. Kaplan–Meier survival analysis assessed prognostic relevance. Functional enrichment and protein–protein interaction (PPI) networks were examined using ShinyGO, STRING, and GeneMANIA. Single-cell RNA sequencing from the TISCH2 database provided insights into tumour microenvironment (TME) dynamics. Results CTH, CBS, and SQRDL were significantly upregulated in HNSCC tissues, while DAO remained unchanged. Promoter methylation analysis revealed hypomethylation of CTH and SQRDL, suggesting increased expression, while CBS, MPST, and DAO showed hypermethylation, indicating repression. Kaplan–Meier analysis linked high CTH and CAT expression and low DAO expression to poor overall survival. Functional enrichment highlighted roles in cysteine biosynthesis, sulfur metabolism, and oxidative stress. PPI networks interacted with tumour-related proteins, implicating H2S genes in tumour progression. Single-cell RNA sequencing confirmed differential expression across TME cell types, indicating a role in immune modulation. Conclusion H2S regulatory genes play a significant role in HNSCC progression through altered expression and epigenetic regulation. Their association with patient survival and involvement in critical metabolic pathways, suggest potential as prognostic biomarkers and therapeutic targets. Further clinical validation is needed to explore their utility in personalised HNSCC treatment.https://doi.org/10.1186/s43042-025-00715-6H2S regulatory genesHNSCCGene expressionPromoter methylationSurvival analysisTumour microenvironment |
| spellingShingle | Mohamed Rizwan Ghouse Santhakumar Egambaram Arunkumar Ramachandran Rajesh Parsanathan The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment Egyptian Journal of Medical Human Genetics H2S regulatory genes HNSCC Gene expression Promoter methylation Survival analysis Tumour microenvironment |
| title | The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| title_full | The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| title_fullStr | The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| title_full_unstemmed | The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| title_short | The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| title_sort | impact of hydrogen sulfide regulatory gene alterations on head and neck squamous cell carcinoma prognosis and tumor microenvironment |
| topic | H2S regulatory genes HNSCC Gene expression Promoter methylation Survival analysis Tumour microenvironment |
| url | https://doi.org/10.1186/s43042-025-00715-6 |
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