Language

English

Publication Date

9-13-2025

Journal

Current Oncology

DOI

10.3390/curroncol32090512

PMID

41002582

PMCID

PMC12468542

PubMedCentral® Posted Date

9-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Somatostatin receptor 2 (SSTR2), a G protein-coupled receptor, is overexpressed in multiple malignancies, including hepatocellular carcinoma (HCC). While SSTR2 has traditionally been viewed as an inhibitory receptor involved in suppressing hormone secretion and cell proliferation, emerging evidence suggests a more complex role in cancer biology. However, the functional implications of SSTR2 expression in HCC remain poorly understood. This study aimed to systematically investigate the molecular landscape associated with SSTR2 expression in HCC and evaluate its potential as a therapeutic target.

Methods: SSTR2 expression patterns across 22 tumor types were assessed using TNMplot, and its expression in HCC was further validated through The Human Protein Atlas. Integrative analysis of transcriptomic profiles, protein expression data, and somatic copy number alterations was performed using data from The Cancer Genome Atlas (TCGA) to stratify HCC patients by SSTR2 expression levels. Gene Ontology (GO) enrichment analysis was conducted via SRplot to uncover biological processes and signaling pathways associated with SSTR2. Kaplan-Meier survival analyses were performed using GEO datasets to determine the prognostic significance of SSTR2 expression.

Results: SSTR2 is moderately expressed in the majority of HCC tumors. Elevated SSTR2 expression correlates with significantly poorer overall and disease-specific survival. High SSTR2 levels are associated with activation of oncogenic signaling cascades related to cell proliferation, epithelial-to-mesenchymal transition (EMT), angiogenesis, and metastasis. Additionally, SSTR2 expression is positively correlated with several receptor tyrosine kinases and oncogenes implicated in HCC progression.

Conclusions: Our findings suggest that SSTR2 is not merely a passive biomarker but may contribute to HCC pathogenesis through modulation of oncogenic pathways. These data support the rationale for further development of SSTR2-directed therapeutic strategies to inhibit tumor growth and invasion in HCC patients.

Keywords

Humans, Receptors, Somatostatin, Carcinoma, Hepatocellular, Liver Neoplasms, Prognosis, Gene Expression Regulation, Neoplastic, hepatocellular carcinoma, SSTR2, tumorigenesis, overall survival

Published Open-Access

yes

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