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Machine learning driven multiomics analysis identifies disulfidptosis associated molecular subtypes in ovarian cancer
Qiaoying Jin1,2, Zhaobin Chang1, Jinyi Liu3
1School of Information Science and Engineering, Lanzhou University, Lanzhou, 730000, China.
Abstract:
Precision oncology enables molecularly guided cancer therapy through multi-omics profiling, AI-driven classification, and biomarker-targeted interventions. Disulfidptosis has emerged as a promising therapeutic target, yet no ovarian cancer classification system currently incorporates this mechanism. The sequencing data of the samples in this study were obtained from TCGA and GEO databases. We analyzed 76 genes associated with disulfidptosis and performed consensus clustering based on their expression profiles to stratify the samples into two molecular subtypes. Differentially expressed genes (DEGs) were identified by comparing ovarian cancer tissues with normal samples. LASSO regression and random forest algorithms were then applied to screen marker genes that significantly influenced the clustering outcome. Ultimately, Ten disulfidptosis-related genes were ultimately selected to construct the predictive model. Single-cell sequencing was employed to characterize the tumor-specific expression patterns of key biomarkers. Digital spatial pathology analysis precisely mapped therapeutic target regions within tumor architectures. Immunohistochemical validation ultimately yielded clinically translatable biomarkers with diagnostic and therapeutic potential. Analysis of 76 disulfidptosis-related genes in ovarian cancer (OV) identified two molecular subtypes with distinct genomic profiles, tumor microenvironment characteristics, m6A regulator expression patterns, and clinical outcomes. Subgroup 1 showed copy number gains and immunosuppression, while Subgroup 2 exhibited higher tumor mutational burden (TMB) and immune activation. Subgroup 2 exhibited significantly higher immune infiltration, along with upregulated immune checkpoints. A 10-gene signature and CNN+GRU classifier robustly stratified patients. Single-cell and spatial transcriptomics confirmed epithelial-specific overexpression of key genes. This study identified a 10-gene signature related to disulfidptosis that is associated with distinct tumor microenvironment features, molecular heterogeneity, m6A modification patterns, and immune infiltration characteristics in ovarian cancer. Through multi-omics analyses-including single-cell and spatial transcriptomics-along with protein-level validation, our findings provide insights into the molecular landscape of ovarian cancer and suggest potential targets for future investigation into subtype-specific treatment strategies. All relevant code and analysis pipelines are publicly available at https://github.com/jinqy-lzu/Molecular_Subgroups_OV.git .
Insights
This study identifies two molecular subtypes of ovarian cancer based on disulfidptosis-related genes, revealing distinct tumor microenvironment and immune profiles. A 10-gene signature offers potential for subtype-specific precision oncology strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Precision oncology utilizes multi-omics profiling for targeted cancer therapies.
- Disulfidptosis is a novel therapeutic target, but its role in ovarian cancer (OV) remains unclassified.
- Current ovarian cancer classifications lack integration of disulfidptosis mechanisms.
Purpose of the Study:
- To classify ovarian cancer based on disulfidptosis-related genes.
- To identify molecular subtypes with distinct characteristics and clinical outcomes.
- To develop a predictive model for ovarian cancer stratification.
Main Methods:
- Consensus clustering of 76 disulfidptosis-related genes from TCGA and GEO data.
- Identification of differentially expressed genes (DEGs) and screening using LASSO regression and random forest.
- Construction of a 10-gene predictive model and validation using single-cell and spatial transcriptomics, and immunohistochemistry.
Main Results:
- Two molecular subtypes of ovarian cancer were identified with distinct genomic profiles, tumor microenvironment (TME) features, and m6A regulator expression.
- Subtype 1 exhibited copy number gains and immunosuppression; Subtype 2 showed higher tumor mutational burden (TMB) and immune activation with increased immune infiltration.
- A 10-gene signature and CNN+GRU classifier demonstrated robust patient stratification. Epithelial-specific overexpression of key genes was confirmed.
Conclusions:
- Disulfidptosis-related genes define distinct molecular subtypes in ovarian cancer with varying TME and immune infiltration characteristics.
- The identified 10-gene signature and classification model provide insights into molecular heterogeneity and potential for subtype-specific therapeutic strategies.
- Multi-omics analyses and protein-level validation offer clinically translatable biomarkers for ovarian cancer diagnosis and treatment.

