Multi‑omics identification of a novel signature for serous ovarian carcinoma in the context of 3P medicine and based on twelve programmed cell death patterns: a multi-cohort machine learning study

Mol Med. 2025 Jan 8;31(1):5. doi: 10.1186/s10020-024-01036-x.

Abstract

Background: Predictive, preventive, and personalized medicine (PPPM/3PM) is a strategy aimed at improving the prognosis of cancer, and programmed cell death (PCD) is increasingly recognized as a potential target in cancer therapy and prognosis. However, a PCD-based predictive model for serous ovarian carcinoma (SOC) is lacking. In the present study, we aimed to establish a cell death index (CDI)-based model using PCD-related genes.

Methods: We included 1254 genes from 12 PCD patterns in our analysis. Differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were screened. Subsequently, 14 PCD-related genes were included in the PCD-gene-based CDI model. Genomics, single-cell transcriptomes, bulk transcriptomes, spatial transcriptomes, and clinical information from TCGA-OV, GSE26193, GSE63885, and GSE140082 were collected and analyzed to verify the prediction model.

Results: The CDI was recognized as an independent prognostic risk factor for patients with SOC. Patients with SOC and a high CDI had lower survival rates and poorer prognoses than those with a low CDI. Specific clinical parameters and the CDI were combined to establish a nomogram that accurately assessed patient survival. We used the PCD-genes model to observe differences between high and low CDI groups. The results showed that patients with SOC and a high CDI showed immunosuppression and hardly benefited from immunotherapy; therefore, trametinib_1372 and BMS-754807 may be potential therapeutic agents for these patients.

Conclusions: The CDI-based model, which was established using 14 PCD-related genes, accurately predicted the tumor microenvironment, immunotherapy response, and drug sensitivity of patients with SOC. Thus this model may help improve the diagnostic and therapeutic efficacy of PPPM.

Keywords: Cell death index; Predictive model; Predictive preventive and personalized medicine (PPPM/3PM); Programmed cell death; Serous ovarian carcinoma.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Cohort Studies
  • Computational Biology / methods
  • Cystadenocarcinoma, Serous* / genetics
  • Cystadenocarcinoma, Serous* / mortality
  • Cystadenocarcinoma, Serous* / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genomics / methods
  • Humans
  • Machine Learning*
  • Middle Aged
  • Multiomics
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Precision Medicine / methods
  • Prognosis
  • Transcriptome*

Substances

  • Biomarkers, Tumor