Zhang Xu, Zhao Chenglei, Liu Tianyi
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Department of Computed Tomography, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Discov Oncol. 2025 May 13;16(1):752. doi: 10.1007/s12672-025-02598-w.
Hepatocellular carcinoma (HCC) stands as the fourth leading cause of cancer-related deaths worldwide. SUMO-specific peptidases, known as SENPs, emerge as critical players, regulating tumorigenesis and progression of numerous cancer types. Despite this, the specific impact of SENPs in HCC remains unclear. Hence, our study aimed to reveal the immune and prognostic implications of SENPs in HCC.
The gene expression of SENP in various cancers was examined using open-access databases including TCGA, GTEx, and CPTAC. In order to investigate the prognostic potential of the SENP family, Kaplan-Meier analysis was used. To clarify the underlying biological mechanisms, gene set enrichment analysis (GSEA) was carried out. cBioPortal database was used to evaluate genetic mutation profiles. For insight into the relationship between SENP genes and tumor immunity, various algorithms were used.
Our findings showed that SENP1, SENP2, SENP3, SENP5, SENP6, and SENP7 expression levels were significantly higher in HCC tumor tissues compared to normal tissues. In HCC patients, elevated SENP1 and SENP5 expression has been associated with tumor development and poor outcomes. Our immune infiltration patterns results also showed significant correlations between SENP5 expression and neutrophil (cor = 0.346, p < 0.001), myeloid dendritic cell (cor = 0.491, p < 0.001), macrophage (cor = 0.465, p < 0.001), and memory B cell (cor = 0.336, p < 0.001) infiltration in HCC, whereas SENP1 expression was associated with none of these infiltrations.
The prognostic and immunogenetic value of SENP1 and SENP5 in HCC was demonstrated in this study. Therefore, these two genes have the potential to function as separate prognostic biomarkers and offer promise as immunotherapeutic targets in the fight against HCC.
肝细胞癌（HCC）是全球癌症相关死亡的第四大主要原因。SUMO特异性蛋白酶，即SENPs，是关键参与者，调节多种癌症类型的肿瘤发生和进展。尽管如此，SENPs在HCC中的具体影响仍不清楚。因此，我们的研究旨在揭示SENPs在HCC中的免疫和预后意义。
使用包括TCGA、GTEx和CPTAC在内的开放获取数据库检查SENP在各种癌症中的基因表达。为了研究SENP家族的预后潜力，使用了Kaplan-Meier分析。为了阐明潜在的生物学机制，进行了基因集富集分析（GSEA）。使用cBioPortal数据库评估基因突变谱。为了深入了解SENP基因与肿瘤免疫之间的关系，使用了各种算法。
我们的研究结果表明，与正常组织相比，HCC肿瘤组织中SENP1、SENP2、SENP3、SENP5、SENP6和SENP7的表达水平显著更高。在HCC患者中，SENP1和SENP5表达升高与肿瘤发展和不良预后相关。我们的免疫浸润模式结果还显示，SENP5表达与HCC中的中性粒细胞（cor = 0.346，p < 0.001）、髓样树突状细胞（cor = 0.491，p < 0.001）、巨噬细胞（cor = 0.465，p < 0.001）和记忆B细胞（cor = 0.336，p < 0.001）浸润之间存在显著相关性，而SENP1表达与这些浸润均无关。
本研究证明了SENP1和SENP5在HCC中的预后和免疫遗传学价值。因此，这两个基因有可能作为独立的预后生物标志物发挥作用，并有望成为对抗HCC的免疫治疗靶点。
