Background Gastric cancer (GC) is one of the leading causes of cancer-related deaths, particularly in early-stage GC, which is frequently asymptomatic, and there are no reliable molecular markers available for diagnosis. Purpose To identify potential candidate genomic biomarkers for GC with respect to genetic variations and expression changes in genes related to hydrogen sulfide (H2S) metabolism and antioxidant defence. Methodology We included 15 patients with newly diagnosed gastric adenocarcinoma in a paired case-control molecular design based on tumour tissue and adjacent histologically normal gastric mucosa. Biopsy tissues were used to extract genomic DNA and total RNA. Complementary DNA (cDNA) was synthesised, followed by standard polymerase chain reaction, Sanger sequencing, and quantitative real-time polymerase chain reaction analysis. The selected target genes were cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (MPST), catalase (CAT), and glutathione peroxidase 1 (GPX1). Results A total of 53 insertion/deletion/duplication variants without amino acid change and 11 predicted amino acid-changing sites plus multiple homozygous substitution variants were identified through sequence variants screening. Most variants were heterozygous and not present in external databases. Common high-frequency variants included CBS 19,430 C > CG, CTH 28400G > GT, CAT 33470G > GA, and changes associated with GPX1613_618delGGCGGC. Expression analysis indicated upregulation of CBS, CAT, and GPX1 (by approximately 1.40-, 1.73-, and 1.93-fold, respectively), downregulation of MPST (3.11-fold), and slight downregulation of CTH. Conclusion Somatic mutations and altered expression of CBS, CTH, MPST, CAT, and GPX1 in GC tissues indicate coordinated remodeling of sulfur metabolism and redox-defence pathways. Nevertheless, the low ROC performance suggests that these genes should not yet be viewed as viable solo diagnostic biomarkers. Instead, they are exploratory molecular signatures and candidate markers that must be validated on larger series of independent patients, matched tumour-normal sequencing, protein/enzyme lateral re-confirmation and functional studies.

Exploratory profiling of oxidative stress and hydrogen sulfide synthesis gene expression and sequence variants in gastric cancer patients

期刊论文
发表日期：

2026年7月27日

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Ali Zainal Omar,
Abbas Burhan Salihi,
Abdullah Saeed Delmany

摘要

Background

Gastric cancer (GC) is one of the leading causes of cancer-related deaths, particularly in early-stage GC, which is frequently asymptomatic, and there are no reliable molecular markers available for diagnosis.

Purpose

To identify potential candidate genomic biomarkers for GC with respect to genetic variations and expression changes in genes related to hydrogen sulfide (H₂S) metabolism and antioxidant defence.

Methodology

We included 15 patients with newly diagnosed gastric adenocarcinoma in a paired case-control molecular design based on tumour tissue and adjacent histologically normal gastric mucosa. Biopsy tissues were used to extract genomic DNA and total RNA. Complementary DNA (cDNA) was synthesised, followed by standard polymerase chain reaction, Sanger sequencing, and quantitative real-time polymerase chain reaction analysis. The selected target genes were cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CTH), 3-mercaptopyruvate sulfurtransferase (MPST), catalase (CAT), and glutathione peroxidase 1 (GPX1).

Results

A total of 53 insertion/deletion/duplication variants without amino acid change and 11 predicted amino acid-changing sites plus multiple homozygous substitution variants were identified through sequence variants screening. Most variants were heterozygous and not present in external databases. Common high-frequency variants included CBS 19,430 C > CG, CTH 28400G > GT, CAT 33470G > GA, and changes associated with GPX1613_618delGGCGGC. Expression analysis indicated upregulation of CBS, CAT, and GPX1 (by approximately 1.40-, 1.73-, and 1.93-fold, respectively), downregulation of MPST (3.11-fold), and slight downregulation of CTH.

Conclusion

Somatic mutations and altered expression of CBS, CTH, MPST, CAT, and GPX1 in GC tissues indicate coordinated remodeling of sulfur metabolism and redox-defence pathways. Nevertheless, the low ROC performance suggests that these genes should not yet be viewed as viable solo diagnostic biomarkers. Instead, they are exploratory molecular signatures and candidate markers that must be validated on larger series of independent patients, matched tumour-normal sequencing, protein/enzyme lateral re-confirmation and functional studies.