J Proteome Res. 2025 Dec 30. doi: 10.1021/acs.jproteome.5c00741. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) ranks among the most common causes of cancer-related deaths globally. The high incidence of HCC is largely linked to chronic hepatitis virus infections, liver cirrhosis, and exposure to carcinogenic substances. Egypt has one of the world's highest burdens of HCC, with liver cirrhosis from chronic hepatitis C virus (HCV) infection as the primary risk factor. Malignant conversion of cirrhosis to HCC is often fatal in part because adequate biomarkers are not available for diagnosis of HCC in the early stage. Therefore, there is a critical need for more effective biomarkers to detect HCC at an early stage, when therapeutic intervention is more likely to be successful. Multiomics integration has emerged as a powerful strategy to uncover biomarkers and better understand the molecular underpinnings of complex diseases such as HCC. This study summarizes findings from multiple untargeted and targeted mass spectrometry-based analyses of proteins, N-linked glycans, and metabolites performed on blood samples from HCC cases and cirrhotic cohorts recruited in Egypt. Integrative analysis using machine learning methods is performed to identify a panel of multiomics features that differentiates HCC cases from the high-risk population of cirrhotic patients with liver cirrhosis.

PMID:41467861 | DOI:10.1021/acs.jproteome.5c00741

Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11254134.

ABSTRACT

The complexity of biological systems and the limitations of analyzing individual omics studies for biomarker discovery have raised the need for a holistic approach by multi-omics integration. By integrating data from multiple layers, researchers can gain insights into the entire system rather than just individual components. Also, integrative analysis can help identify molecular signatures that are more accurate in predicting disease onset, progression, and response to treatment, leading to better-targeted therapies and personalized medicine. In this paper, we explored statistical and deep learning methods for integrative analysis of metabolomics, lipidomics, peptidomics, proteomics, and glycoproteomics data acquired by LC-MS/MS analysis of serum samples from 20 hepatocellular carcinoma (HCC) cases and 20 patients with liver cirrhosis (CIRR). The goal is to identify a panel of multi-omics features that distinguish HCC cases from cirrhotic controls. A pathway analysis using these features identified biological pathways such as LXR/RXR Activation and Acute Response signaling as significantly enriched in our multi-omics datasets.

PMID:41336317 | PMC:PMC12694951 | DOI:10.1109/EMBC58623.2025.11254134

Metabolites. 2025 Aug 28;15(9):575. doi: 10.3390/metabo15090575.

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, ranks as the third leading cause of mortality globally. Patients diagnosed with HCC exhibit a dismal prognosis mostly due to the emergence of symptoms in the advanced stages of the disease. Moreover, conventional biomarkers demonstrate insufficient efficacy in the early detection of HCC, hence highlighting the need for the identification of novel and more effective biomarkers.

METHODS: In this paper, we investigate methods for integration of multi-omics data we generated by both untargeted and targeted mass spectrometric analysis of serum samples from HCC cases and patients with liver cirrhosis. Specifically, the performances of several feature selection methods are evaluated on their abilities to identify a panel of multi-omics features that distinguish HCC cases from cirrhotic controls.

RESULTS: The integrative analysis identified key molecules associated with liver including such as leucine and isoleucine as well as SERPINA1, which is involved in LXR/RXR Activation and Acute Response signaling. A new method that uses recursive feature selection in conjunction with a transformer-based deep learning model as an estimator led to more promising results compared to other deep learning methods that perform disease classification and feature selection sequentially.

CONCLUSIONS: The findings in this study reinforce the importance of adapting or extending deep learning models to support robust feature selection, especially for integration of multi-omics data with limited sample size to avoid the risk of overfitting and the need for evaluation of the multi-omics features discovered in this study via blood samples from a larger and independent cohort to identify robust biomarkers for HCC.

PMID:41002959 | PMC:PMC12471784 | DOI:10.3390/metabo15090575