Circulatory Agrin Serves as a Prognostic Indicator for Hepatocellular Carcinoma
by
Ankita Kapoor
1,†,
Reza Bayat Mokhtari
2,†,
Sahithi Savithri Sonti
1,
Riya Patel
1,
Anthony George
3,
Kristopher Attwood
3,
Renuka Iyer
1,* and 
Sayan Chakraborty
2,4,*
1
Department of Hematology-Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
3
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
4
Program of Developmental Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2024, 16(15), 2719; https://doi.org/10.3390/cancers16152719
Submission received: 20 June 2024
/
Revised: 26 July 2024
/
Accepted: 30 July 2024
/
Published: 31 July 2024
(This article belongs to the Special Issue Liver Cancers Molecular Biomarkers Predicting Outcome)
Simple Summary
There is an unmet need for the discovery of new biomarkers for detection and prognosis of liver cancers. Here we reveal the clinical potential of agrin as a key circulatory protein that predicts overall outcomes of liver cancer patients regardless of treatment regimens. Together, our study lays the foundation for further evaluation of agrin as a biomarker for improved clinical management of liver cancers.
Abstract
Hepatocellular carcinoma (HCC), the predominant form of liver cancer, is associated with high mortality rates both in the United States and globally. Despite current advances in immunotherapy regimens, there is a scarcity of biomarkers to guide therapy selection. Alpha-fetoprotein (AFP) and glypican-3 have been proposed as biomarkers for HCC, but they do not provide any prognostic benefit for modeling disease progression. Agrin, a secreted proteoglycan, is frequently overexpressed in HCC and plays prominent role(s) in the liver tumor microenvironment (TME) to promote hepatocarcinogenesis. Here we employed a pilot single-center retrospective investigation to assess the prognostic value of agrin in HCC. Our evidence suggests that elevated serum agrin levels are associated with poor prognosis and performance among HCC patients. Multivariate Cox regression models indicate that secreted agrin serves as a better prognostic indicator compared to AFP that is significantly correlated with other secreted biomarkers (e.g., IL6). Cumulatively, this work demonstrates a promising clinical value of agrin in the detection and prognosis of HCC.
Keywords:
agrin; hepatocellular carcinoma; prognosis; biomarker; extracellular matrix
