Journal Article

Machine learning driven multiomics analysis identifies disulfidptosis associated molecular subtypes in ovarian cancer

Chang, Zhaobin, Liu, Jinyi, Lu, Yonggang, Yang, Luxi, Jin, Qiaoying, Liu, Yali

2025

Overview

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 .

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/114 / 631/208 / 631/337 / 692/53 / Algorithms / Artificial intelligence / Bioinformatics / Biological analysis / Biomarkers / Biomarkers, Tumor - genetics / Cancer therapies / Cell death / Chemical bonds / Classification / Clustering / Copy number / Deep learning / Diagnosis / Disulfidptosis / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Genomics / Genomics - methods / Glucose / Heterogeneity / Humanities and Social Sciences / Humans / Immune checkpoint / Immune microenvironment / Immune response / Immunosuppression / Infiltration / Machine Learning / Medical research / Metabolism / Metastases / Multi-omics / multidisciplinary / Multiomics / N6-methyladenosine / Ovarian cancer / Ovarian Neoplasms - classification / Ovarian Neoplasms - genetics / Ovarian Neoplasms - metabolism / Ovarian Neoplasms - pathology / Precision medicine / Prediction models / Proteins / Science / Science (multidisciplinary) / Single-Cell Analysis / Spatial analysis / Therapeutic targets / Transcriptome / Transcriptomics / Tumor microenvironment / Tumor Microenvironment - genetics / Tumors