Work

The Impact of Hydrogen Sulfide Regulatory Gene Alterations on Head and neck squamous cell carcinoma prognosis and tumor microenvironment

Year: 2025

Type: article

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.

Source: Egyptian Journal of Medical Human Genetics

DOI: 10.1186/s43042-025-00715-6

Authors: Mohamed Rizwan Ghouse, Santhakumar Egambaram, Arunkumar Ramachandran, Rajesh Parsanathan

Institutions: Central University of Tamil Nadu, Madras Medical College

Language: English

Topic: Sulfur Compounds in Biology

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Central University of Tamil Nadu, Department of Biotechnology, Ministry of Science and Technology, India, Department of Science and Technology, Ministry of Science and Technology, India