Ensemble machine learning algorithms leveraged on serum proteomics for enhanced early detection of ovarian cancer

Ovarian cancer poses a significant clinical challenge due to its asymptomatic onset and poor prognosis, highlighting the critical need for effective early detection strategies. This study developed a framework that integrates serum proteomic profiling with machine learning algorithms. Serum samples from 188 patients and 208 healthy controls were analysed via Matrix-Assisted Laser Desorption/Ionization Time - of - Flight (MALDI - TOF) mass spectrometry, revealing 43 differentially expressed peptides (17 upregulated, 26 downregulated). An ensemble pipeline incorporating eight machine learning algorithms showed favorable discriminatory ability in the study cohort, with the area under the receiver operating characteristic curve (AUC) of the integrated models approaching 1.00 for distinguishing ovarian cancer samples from healthy controls. We identified three consensus biomarkers [mass-to-charge ratio (m/z) = 4211.41, 2881.50, 2662.15] through feature importance analysis, and their diagnostic reliability was supported by receiver operating characteristic curves optimization and decision curve analysis. Interpretability approaches integrating Shapley values and LIME indicated that the model's high performance (AUC ≈ 1) was driven by robust multi-dimensional feature contributions. Cross-referencing with existing datasets suggested the PDE11A as a potential diagnostic biomarker. Collectively, this ensemble machine learning algorithms leveraged on serum proteomics shows promising potential for early detection of ovarian cancer, offering a strategy to mitigate the limitations of single-analyte biomarkers.