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Multi-Omics Feature Selection to Identify Biomarkers for Hepatocellular Carcinoma.

Rency S Varghese1, Xinran Zhang1, Sarada Giridharan1

  • 1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.

Metabolites
|September 26, 2025
PubMed
Summary

This study identifies key molecules like leucine, isoleucine, and SERPINA1 for early hepatocellular carcinoma (HCC) detection. A novel deep learning method shows promise for multi-omics data analysis in liver cancer biomarker discovery.

Keywords:
LC-MS/MSdeep learningfeature selectionliver cancermachine learningmulti-omics approaches

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Area of Science:

  • Biomarker discovery
  • Liver cancer research
  • Multi-omics data integration

Background:

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
  • Late-stage diagnosis and inadequate biomarkers hinder effective early detection and treatment of HCC.
  • Novel biomarkers are crucial for improving patient prognosis and survival rates.

Purpose of the Study:

  • To identify a panel of multi-omics features distinguishing HCC from liver cirrhosis using serum samples.
  • To evaluate and compare various feature selection methods for multi-omics data integration.
  • To develop and assess a novel deep learning approach for HCC biomarker discovery.

Main Methods:

  • Untargeted and targeted mass spectrometry were used to generate multi-omics data from serum samples of HCC and cirrhotic patients.
  • Recursive feature selection combined with a transformer-based deep learning model was employed for feature identification.
  • Performance evaluation of different feature selection techniques was conducted to identify HCC-specific markers.

Main Results:

  • Key molecules including leucine, isoleucine, and SERPINA1 were identified as significantly associated with liver cancer.
  • SERPINA1 is implicated in LXR/RXR Activation and Acute Response signaling pathways.
  • The novel recursive feature selection and transformer-based deep learning method outperformed other sequential deep learning approaches.

Conclusions:

  • The study highlights the potential of integrating multi-omics data with advanced deep learning models for robust biomarker discovery in HCC.
  • Adapting deep learning models for feature selection is essential to mitigate overfitting risks with limited sample sizes.
  • Further validation of the discovered multi-omics features in larger, independent cohorts is recommended for robust HCC biomarker identification.