miR-98-5p, miR-130a-3p, and miR-1246 Profiling in Tissue and Liquid Biopsies of Patients with Hepatocellular Carcinoma
4 affiliations
- 1Department of Molecular and Translational Medicine, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy
- 2Department of Clinical and Experimental Sciences, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy
- 3Hepatology Unit, ASST Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy
- 4Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, often arising in cirrhosis. Its early non-invasive diagnosis and prognostic assessment remain challenging due to the limited availability of reliable circulating biomarkers, creating the need to establish non-invasive biomarkers that distinguish malignant transformation. This preliminary study aimed to: discover EV-associated miRNAs that differ among healthy subjects, patients with liver cirrhosis, and patients with HCC; validate selected candidates by ddPCR in an independent cohort; compare their abundance in plasma-derived EVs, whole plasma, and paired tumoral/peritumoral tissues; and explore their diagnostic performance for HCC versus cirrhosis and their associations with clinical outcomes. Methods: miRNA sequencing was performed on plasma-derived EVs from an exploratory cohort of 10 healthy subjects, 10 cirrhotic patients, and 10 HCC patients. Three candidate miRNAs, miR-98-5p, miR-130a-3p, and miR-1246, were subsequently quantified by droplet digital PCR (ddPCR) in an independent cohort of 29 HCC patients, 30 cirrhotic patients, and 20 healthy subjects using plasma-derived EVs, plasma, and paired tumoral/peritumoral liver tissues. Results: In plasma EVs, miR-98-5p and miR-130a-3p were reduced in HCC and cirrhotic patients compared with healthy subjects, whereas miR-1246 was increased in HCC compared with cirrhosis. In plasma, all three miRNAs were elevated in HCC compared with cirrhosis and healthy controls. Plasma miR-1246 showed the highest diagnostic performance to discriminate HCC from cirrhosis (AUC = 0.87). In tissue, miR-98-5p was upregulated and miR-130a-3p downregulated in tumoral versus peritumoral samples, whereas miR-1246 showed no significant difference. Higher plasma miR-130a-3p and miR-1246 levels were associated with improved overall survival, while increased miR-98-5p levels were associated with lower relapse rates. Conclusions: Among the three miRNAs, plasma miR-1246 showed the strongest diagnostic performance for distinguishing HCC from liver cirrhosis. Combination with miR-98-5p and/or miR-130a-3p did not improve discrimination. Thus, plasma miR-1246 emerged as the leading candidate diagnostic indicator in the HCC cohort, whereas the three miRNAs showed distinct potential associations with prognosis.
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BibTeX
@article{maffezzoni2026mir985p,
title = {{miR-98-5p, miR-130a-3p, and miR-1246 Profiling in Tissue and Liquid Biopsies of Patients with Hepatocellular Carcinoma}},
author = {Martina Maffezzoni and Ilaria Grossi and Iulia Andreea Pelisenco and Chiara Magri and Sarah Molfino and Giovanni Battista Contessi and Nazario Portolani and Giuseppina De Petro and Flora Guerra and Alessandro Salvi},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203379},
url = {https://www.mdpi.com/2072-6694/18/20/3379},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - miR-98-5p, miR-130a-3p, and miR-1246 Profiling in Tissue and Liquid Biopsies of Patients with Hepatocellular Carcinoma
AU - Martina Maffezzoni
AU - Ilaria Grossi
AU - Iulia Andreea Pelisenco
AU - Chiara Magri
AU - Sarah Molfino
AU - Giovanni Battista Contessi
AU - Nazario Portolani
AU - Giuseppina De Petro
AU - Flora Guerra
AU - Alessandro Salvi
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203379
UR - https://www.mdpi.com/2072-6694/18/20/3379
AB - Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, often arising in cirrhosis. Its early non-invasive diagnosis and prognostic assessment remain challenging due to the limited availability of reliable circulating biomarkers, creating the need to establish non-invasive biomarkers that distinguish malignant transformation. This preliminary study aimed to: discover EV-associated miRNAs that differ among healthy subjects, patients with liver cirrhosis, and patients with HCC; validate selected candidates by ddPCR in an independent cohort; compare their abundance in plasma-derived EVs, whole plasma, and paired tumoral/peritumoral tissues; and explore their diagnostic performance for HCC versus cirrhosis and their associations with clinical outcomes. Methods: miRNA sequencing was performed on plasma-derived EVs from an exploratory cohort of 10 healthy subjects, 10 cirrhotic patients, and 10 HCC patients. Three candidate miRNAs, miR-98-5p, miR-130a-3p, and miR-1246, were subsequently quantified by droplet digital PCR (ddPCR) in an independent cohort of 29 HCC patients, 30 cirrhotic patients, and 20 healthy subjects using plasma-derived EVs, plasma, and paired tumoral/peritumoral liver tissues. Results: In plasma EVs, miR-98-5p and miR-130a-3p were reduced in HCC and cirrhotic patients compared with healthy subjects, whereas miR-1246 was increased in HCC compared with cirrhosis. In plasma, all three miRNAs were elevated in HCC compared with cirrhosis and healthy controls. Plasma miR-1246 showed the highest diagnostic performance to discriminate HCC from cirrhosis (AUC = 0.87). In tissue, miR-98-5p was upregulated and miR-130a-3p downregulated in tumoral versus peritumoral samples, whereas miR-1246 showed no significant difference. Higher plasma miR-130a-3p and miR-1246 levels were associated with improved overall survival, while increased miR-98-5p levels were associated with lower relapse rates. Conclusions: Among the three miRNAs, plasma miR-1246 showed the strongest diagnostic performance for distinguishing HCC from liver cirrhosis. Combination with miR-98-5p and/or miR-130a-3p did not improve discrimination. Thus, plasma miR-1246 emerged as the leading candidate diagnostic indicator in the HCC cohort, whereas the three miRNAs showed distinct potential associations with prognosis.
SN - 2072-6694
ER -