Identification of a Novel Lipidomic Biomarker for Hepatocyte Carcinoma Diagnosis: Advanced Boosting Machine Learning Techniques Integrated with Explainable Artificial Intelligence


Yagin F. H., ÇOLAK C., Al-Hashem F., Alzakari S. A., Alhussan A. A., Aghaei M.

Metabolites, vol.15, no.11, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 11
  • Publication Date: 2025
  • Doi Number: 10.3390/metabo15110716
  • Journal Name: Metabolites
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, Directory of Open Access Journals
  • Keywords: biomarkers, explainable boosting machine, hepatocellular carcinoma, lipidomics, machine learning
  • Inonu University Affiliated: Yes

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, often diagnosed at late stages due to the limited sensitivity of current screening tools. This study explores whether blood-based lipidomic profiling, combined with explainable artificial intelligence (XAI), can improve early and interpretable detection of HCC. Methods: We analyzed lipidomic data from 219 HCC patients and 219 matched healthy controls using liquid chromatography-mass spectrometry. An Explainable Boosting Machine (EBM) was employed to identify discriminatory lipid biomarkers and was compared against several standard machine learning algorithms. Results: The EBM model achieved superior performance with 87.0% accuracy, 87.7% sensitivity, 86.3% specificity, and an AUC of 91.8%, outperforming other models. Key lipid biomarkers identified included specific phosphatidylcholines (PC 38:2, PC 40:4), sphingomyelins (SM d40:2 B), and lysophosphatidylcholines (LPC 18:2), which exhibited significant alterations in HCC patients and highlighted disruptions in sphingolipid metabolism. Conclusions: Integration of lipidomics with explainable machine learning offers a powerful, transparent approach for HCC biomarker discovery, achieving high diagnostic accuracy while providing biological insights. This strategy holds promise for developing non-invasive, clinically interpretable screening tools to improve early detection of liver cancer.