The knowledge accumulated over the past two decades has revealed that the natural history of metabolic dysfunction-associated steatotic liver disease (MASLD) and the drivers of the disease severity are not only complex but also exhibit variation among patients. This intricate clinical scenario entails major therapeutic and management implications. In this review, we provide a comprehensive examination of recent advancements in our understanding of MASLD heterogeneity, drawing insights from multiomics and panomics studies. The discussion herein explores the instrumental role of panomics in MASLD research, elucidating the potential for the identification of molecular subtypes that exhibit divergent survival outcomes or heterogeneous responses to various treatments. Furthermore, we provide insights into the challenges in addressing disease heterogeneity and potential solutions. Finally, the most advanced technological advancements and prospective research directions in the domain of MASLD research are delineated, with the objective of facilitating the implementation of personalized diagnosis and interventions.
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Semaglutide in MASH with F2-F3 fibrosis: a holistic perspective on the ESSENCE phase 3 trial Carlos Jose Pirola, Silvia Sookoian Metabolism and Target Organ Damage.2026;[Epub] CrossRef
Mapping the genomic landscape of MASLD: A framework for molecular subtyping and precision hepatology Carlos José Pirola, Silvia Sookoian Med.2026; : 101131. CrossRef
Background/Aims Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers.
Methods We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses.
Results Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types.
Conclusions Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.
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Carbonic anhydrase 9 as a circulating biomarker and therapeutic target in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab Yu Sato, Takahiro Kodama, Kazuki Maesaka, Machiko Kai, Kazuhiro Murai, Yuki Tahata, Yoshinobu Saito, Tasuku Nakabori, Kazuyoshi Ohkawa, Satoshi Tanaka, Ryotaro Sakamori, Masanori Miyazaki, Kunimaro Furuta, Hisashi Ishida, Kengo Matsumoto, Seiichi Tawara, Journal for ImmunoTherapy of Cancer.2026; 14(4): e013384. CrossRef
Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer Pooja Singh, Yashika W. Dhir, Shagun Gupta, Ankur Kaushal, Deepak Kala, Rupak Nagraiik, Naveen K. Kaushik, Md Salik Noorani, Abdul R. Asif, Bharat Singh, Shahbaz Aman, Sunny Dhir 3 Biotech.2025;[Epub] CrossRef
Development of a big data platform for collecting and utilizing clinical information from the Korea Biobank Network Yun Seon Im, Seol Whan Oh, Ki Hoon Kim, Wona Choi, In Young Choi BMC Medical Informatics and Decision Making.2025;[Epub] CrossRef
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Unveiling etiology-specific blood biomarkers in hepatocellular carcinoma: A gateway to personalized medicine: Editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma” Joseph C. Ahn, Ju Dong Yang Clinical and Molecular Hepatology.2024; 30(4): 689. CrossRef
Technology and Future of Multi-Cancer Early Detection Danny A. Milner, Jochen K. Lennerz Life.2024; 14(7): 833. CrossRef
Correspondence to editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma” Su Bin Lim, Hyo Jung Cho Clinical and Molecular Hepatology.2024; 30(4): 1009. CrossRef
Background/Aims The reactive oxygen species from thioacetamide (TAA) induces rat liver cirrhosis that resembles the human disease, and it can serve as a suitable animal model for studying human liver cirrhosis. The aim of this study was to identify the molecular protein signatures via a proteomics approach with using a rat model with TAA-induced liver cirrhosis. Methods: Male Wistar rats were treated with 0.3 g/L TAA in their drinking water. The animals were then sacrificed at 9 and 30 weeks after TAA administration. The development of liver cirrhosis was observed with histological study. The livers were processed for proteins extraction and the proteins were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and this was validated by immunohistochemical staining. Results: On the proteomics analysis of the liver tissues, a total of 88 proteins showed significant change in their expression between the controls and the cirrhotic rats. When the proteins were categorized by their function, they included ECM/cellular skeleton, cell proliferation/death signal, metabolism, DNA damage/stress and immune response related proteins. The level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6) precursor, transforming growth factor-beta (TGF-β) induced protein, TIMP-1 and MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA, also showed the same increasing pattern. In contrast, the expression level of the proteins did not show a significant change at 9 weeks, but this increased to 3-fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin A2, neurofibromatosis type 2 and aldehyde dehydrogenase. Conclusions: This study showed that there is a repertoire of proteins during the development of liver cirrhosis via TAA. In this model, IL-6, TGF-β, MMP-9 and TIMP-1 were reconfirmed as the molecular signatures during the development of TAA-induced liver cirrhosis. (Korean J Hepatol 2006;12:93-102)
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