鞘磷脂磷酸二酯酶4（SMPD4）的高表达促进肝癌发生并与不良预后相关。

High expression of SMPD4 promotes liver cancer and is associated with poor prognosis.

作者信息

Wang Rongyue, Wang Ting, Su Yanze, Lin Zhiheng, Liu Xiaoping, Jiao Yuanjun, Liu Jikui, Chen Erbao

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China.

Department of Clinical Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China.

出版信息

BMC Res Notes. 2025 Apr 10;18(1):159. doi: 10.1186/s13104-025-07212-4.

DOI:10.1186/s13104-025-07212-4

PMID:40211349

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11987469/

Abstract

OBJECTIVES

The expression of sphingomyelin phosphodiesterase 4 (SMPD4), a neutral sphingomyelin enzyme, is intricately associated with tumorigenesis and progression. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study mainly reports the expression, prognostic value and tumor biological function of SMPD4 in HCC.

METHODS

The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression patterns of SMPD4. Survival Analyses using the Kaplan-Meier method were conducted to assess the predictive value of SMPD4 in HCC. Immunohistochemistry method and real-time quantitative PCR were used to analyze the expression of SMPD4 in our clinical cohort. Immune infiltration analysis was performed to explore the correlation between SMPD4 expression and immune cell infiltration in HCC. Functional enrichment analysis was conducted to depict SMPD4-associated functions and pathways. Using human HCC cell lines, we studied the influence of SMPD4 in cell proliferation, invasion and migration.

RESULTS

We found SMPD4 was overexpressed in HCC. The Kaplan-Meier curves demonstrated that higher expression of SMPD4 was associated with worse survival in patients with HCC. Immune infiltration analysis showed that SMPD4 expression exhibited positive correlations with CD4 + T cells, Type 2 T helper cells, and negatively related to neutrophil, eosinophil, nature killer cells, macrophage, activated CD8 T cells. Functional enrichment analysis revealed that SMPD4 expression is associated with cell cycle pathways. Additionally, cell functional studies in HCC cell lines indicated that the knockdown of SMPD4 significantly inhibited cell growth, invasion and migration.

CONCLUSIONS

These results reveal that high SMPD4 expression is associated with poor prognosis and promotes HCC cell proliferation, invasion and migration. SMPD4 is a promising prognostic biomarker with functional significance for HCC.

摘要

目的

中性鞘磷脂酶鞘磷脂磷酸二酯酶4（SMPD4）的表达与肿瘤发生和进展密切相关。然而，其在肝细胞癌（HCC）中的作用仍不清楚。本研究主要报道SMPD4在HCC中的表达、预后价值及肿瘤生物学功能。

方法

利用癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和国际癌症基因组联盟（ICGC）数据库研究SMPD4的表达模式。采用Kaplan-Meier法进行生存分析，以评估SMPD4在HCC中的预测价值。采用免疫组织化学方法和实时定量PCR分析SMPD4在我们临床队列中的表达。进行免疫浸润分析，以探讨SMPD4表达与HCC免疫细胞浸润之间的相关性。进行功能富集分析，以描述与SMPD4相关的功能和通路。利用人HCC细胞系，我们研究了SMPD4对细胞增殖、侵袭和迁移的影响。

结果

我们发现SMPD4在HCC中过表达。Kaplan-Meier曲线表明，SMPD4的高表达与HCC患者较差的生存率相关。免疫浸润分析表明，SMPD4表达与CD4 + T细胞、2型辅助性T细胞呈正相关，与中性粒细胞、嗜酸性粒细胞、自然杀伤细胞、巨噬细胞、活化的CD8 T细胞呈负相关。功能富集分析显示，SMPD4表达与细胞周期通路相关。此外，HCC细胞系中的细胞功能研究表明，敲低SMPD4可显著抑制细胞生长、侵袭和迁移。