Hernandez Vargas Servando, Aghaamiri Solmaz, Adams Jack T, Bateman Tyler M, Acidi Belkacem, Ghosh Sukhen C, Khalaj Vahid, Kaseb Ahmed O, Tran Cao Hop S, Momeny Majid, Azhdarinia Ali
The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Curr Oncol. 2025 Sep 13;32(9):512. doi: 10.3390/curroncol32090512.
(1) 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. (2) 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. (3) 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. (4) 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.
（1）背景：生长抑素受体2（SSTR2）是一种G蛋白偶联受体，在包括肝细胞癌（HCC）在内的多种恶性肿瘤中过表达。虽然传统上认为SSTR2是一种参与抑制激素分泌和细胞增殖的抑制性受体，但新出现的证据表明其在癌症生物学中具有更复杂的作用。然而，SSTR2在HCC中表达的功能意义仍知之甚少。本研究旨在系统地研究与HCC中SSTR2表达相关的分子格局，并评估其作为治疗靶点的潜力。（2）方法：使用TNMplot评估22种肿瘤类型中SSTR2的表达模式，并通过人类蛋白质图谱进一步验证其在HCC中的表达。利用癌症基因组图谱（TCGA）的数据对转录组谱、蛋白质表达数据和体细胞拷贝数改变进行综合分析，以根据SSTR2表达水平对HCC患者进行分层。通过SRplot进行基因本体（GO）富集分析，以揭示与SSTR2相关的生物学过程和信号通路。使用GEO数据集进行Kaplan-Meier生存分析，以确定SSTR2表达的预后意义。（3）结果：大多数HCC肿瘤中SSTR2呈中度表达。SSTR2表达升高与总体生存率和疾病特异性生存率显著降低相关。高SSTR2水平与与细胞增殖、上皮-间质转化（EMT）、血管生成和转移相关的致癌信号级联激活有关。此外，SSTR2表达与HCC进展中涉及的几种受体酪氨酸激酶和癌基因呈正相关。（4）结论：我们的研究结果表明，SSTR2不仅是一个被动的生物标志物，还可能通过调节致癌途径促进HCC的发病机制。这些数据支持进一步开发针对SSTR2的治疗策略以抑制HCC患者肿瘤生长和侵袭的理论依据。
