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. 2025 May 28:17:1533-1545.
doi: 10.2147/IJWH.S515836. eCollection 2025.

Hydrogen Sulfide Expression May Affect Ovarian Cancer Progression and Drug Resistance

Qiong Zhu  1   2 , Yi Liu  3 , Juan Zhou  4 , Miduo Tan  2   5 , Yaxin Xue  6 , Yin Tao  2   7
Affiliations

Hydrogen Sulfide Expression May Affect Ovarian Cancer Progression and Drug Resistance

Qiong Zhu et al. Int J Womens Health. .

Abstract

Objective: The present study aimed to evaluated the expression profiles of the Hydrogen sulfide (H2S)-synthesizing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) expression and attempted to establish its relationship to ovarian cancer (OV) drug resistance and prognosis.

Methods: The expression levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) were analyzed in OV from GSE26193 and GSE14764 datasets, and OVCAR8 cisplatin resistant cell line from GSE45553 datasets. The correlation between prognosis with CBS and CSE expression levels were analyzed in OV from GSE26193 dataset. Immunohistochemical (IHC) analysis of CBS and CSE expression, meanwhile Kaplan-Meier analyzed of corresponding prognosis in OV patients. The relative drug sensitivity of CBS and CSE genes via gene set cancer analysis. Ultimately, the correlations among OV immune cells, CBS, and CSE. The CBS and CSE expression levels, and pan-cancer prognosis using TCGA database.

Results: CBS and CSE were significantly overexpressed in the OV and OVCAR8 cisplatin resistant cell line (GSE26193: p < 0.001 and p < 0.0001; GSE14764: p < 0.001 and p < 0.0001 IHC: p<0.0001 and p<0.0001; GSE45553: p < 0.0001 and p < 0.0001, respectively). Interestingly, CBS is closely associated with OS and PFS in GSE26193 dataset and OV patients (GSE26193: PFS, p = 0.0391; OS, p = 0.0328. OV patients: PFS, p= 0.017; OS, p=0.030). The CBS and CSE expression levels were correlated with immune cells, CD4 T cells, neutrophils, macrophages, and dendritic cells (DC) and their respective infiltration scores significantly differed. Both CBS and CSE expression levels influenced pan-cancer prognosis.

Conclusion: H2S overexpression affected the OS and PFS and could also have an impact on the drug resistance of OV. Pan cancer prognosis may vary with H2S expression.

Keywords: drug resistance; hydrogen sulfide; immune cell; ovarian cancer; pan-cancer; progression.

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Conflict of interest statement

The authors have no known conflicts of interest to declare for this work.

Figures

Figure 1
Figure 1
Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are responsible for the enzymatic production of hydrogen sulfide (H2S).
Figure 2
Figure 2
Workflow of the present study.
Figure 3
Figure 3
The expression and Immunohistochemistry in ovarian cancer. (A–D) The expression of CBS and CSE in GSE14764 and GSE26193 datasets. (E–G) Immunohistochemical detection of CBS and CSE in normal and ovarian cancer tissue ((brown represents CD1a). (H and I) The CBS and CSE expression levels were relatively low in the cisplatin-sensitive OVCAR8 cell line from GSE45553 dataset. (***p < 0.001; ****p < 0.0001).
Figure 4
Figure 4
The expression of CBS and CSE affects the prognosis of ovarian cancer. (A–H) The expression of CBS affects the OS and PFS, while there is no difference in CSE in OV from GSE26193 dataset and ovarian cancer patients.
Figure 5
Figure 5
The correlation between CBS and CSE with immune cells and immune infiltration. (A and B) The Timer method analyzed infiltration with CBS and CSE expression levels. (C and D) The QUANTISEQ method analyzed infiltration with CBS and CSE expression levels. (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001).
Figure 6
Figure 6
CBS and CSE expression levels were associated with drug sensitivity. (A) The drug sensitivity of CBS and CSE were analyzed in the GDSC dataset. (B) The drug sensitivity of CBS and CSE were analyzed in the CTRP dataset.
Figure 7
Figure 7
CBS and CSE are overexpressed in pan-cancer and affect disease prognosis. (A and B) The CBS and CSE expression were evaluated in 36 different cancer types listed in the GTEx and TCGA databases, respectively. (C and D) Association of CBS and CSE expression with prognosis in 36 cancer types listed in the GTEx and TCGA databases. (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001).
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