PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

SPOCK1 in Liver Diseases: From Oncogenic Role to Biomarker Potential

Name of the presenter

Szakadáti Helga

Institute/workplace of the presenter

Semmelweis University, Department of Pathology and Experimental Cancer Research

Authors

Helga Szakadáti¹, Kornélia Baghy¹, Lóránd Váncza¹, Ilona Kovalszky¹

1: Semmelweis University, Department of Pathology and Experimental Cancer Research

Text of the abstract

Introduction
SPOCK1 (SPARC/osteonectin, CWCV, and Kazal-like domain proteoglycan 1) is a conserved, multi-domain proteoglycan with a heparan sulfate/chondroitin-sulfate side chain. While absent in most healthy tissues, its presence in normal liver implies a physiological role. Elevated SPOCK1 expression was observed in various cancers, including hepatocellular carcinoma (HCC). Its intracellular retention suggests a functional change; however, its exact role and mechanism remain unclear.
Aims
Our aim is to uncover the role of SPOCK1 in the liver, its contribution to tumorigenesis and progression, and its significance as a biomarker in liver diseases.
Methods
HepG2 hepatoma cells were transfected with control and SPOCK1-overexpressing plasmids and analyzed using qRT-PCR, automated Western blot, BrdU assay, and immunostaining to explore SPOCK1’s effects on liver cell function. Xenograft model was used for in vivo evaluation. FFPE liver tissues and plasma samples were obtained from patients with various liver malignancies. SPOCK1 plasma levels were detected by ELISA. In silico analysis compared SPOCK1 levels in normal and cancerous liver.
Results
SPOCK1 overexpression activated the Akt-mTOR pathway, enhanced mitotic activity detected by cyclin B1 and p-HH3, and increased DNA synthesis in HepG2 cells. SPOCK1 overexpression significantly enhanced HepG2 cell tumorigenesis in xenograft models. Consistently, FFPE tissues showed significantly higher SPOCK1 levels in all diseases compared to normal liver, especially in HCC and HCV-related cases. Patients with liver cancer exhibited higher plasma SPOCK1 levels than patients with benign or non-tumorous conditions, and SPOCK1 was elevated in fatty liver and NASH cases. However, a considerable decrease was seen in SPOCK1 levels in patients with HBV infections. Supporting these findings, in silico analysis revealed significant SPOCK1 overexpression in liver cancer compared to healthy liver.
Conclusion
Our results show that SPOCK1 overexpression in hepatoma cells promotes cell proliferation, suggesting a role in tumorigenesis. In silico analysis supports SPOCK1 upregulation in liver cancer. Elevated circulating serum SPOCK1 in HCC and CCC, cirrhosis, fatty liver, and NASH indicates its potential as a biomarker, though the decrease related to HBV needs further study.
Funding
This work was supported by NKFI-OTKA FK 138593.