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AP1S1基因在前列腺癌中的表达及其对患者预后影响研究
作者:黄月婷1 2  陈南辉2 3  张桂豪2  江惠明2  黄志成2  谢周洲2 3  彭山森2 3  王炯明2  陈百通2  王文昊4 
单位:1. 广东医科大学 第一临床医学院, 广东 湛江 524000;
2. 梅州市人民医院 泌尿外二科, 广东 梅州 514000;
3. 汕头大学医学院 梅州临床学院, 广东 梅州 514000;
4. 中山大学附属第三医院粤东医院 甲乳外科, 广东 梅州 514000
关键词:前列腺癌 衔接因子相关蛋白复合体1亚基σ1 预后 生物信息学 
分类号:R737.25;R730.7;R857.3
出版年·卷·期(页码):2025·53·第九期(1401-1408)
摘要:

目的: 衔接因子相关蛋白复合体1亚基σ1(AP1S1)是一种参与编码组装衔接蛋白复合体的蛋白编码基因,在调节细胞内外跨膜运输机制上起到关键作用,可影响多种疾病的进展,然而AP1S1在前列腺癌中作用尚未明确,本研究旨在探讨AP1S1对前列腺癌发生发展的潜在影响。方法: 基于GEPIA2、THPA及TCGA数据库分析AP1S1在前列腺癌中的表达水平及其表达高低与总生存(OS)、无病生存(DFS)的关系,并收集梅州市人民医院前列腺癌和非前列腺癌组织各12例,通过 qPCR实验进一步验证AP1S1在前列腺癌中的表达情况。采用Metascape工具进行GO和KEGG富集分析以挖掘AP1S1基因的潜在分子机制;通过R软件分析TCGA数据库中前列腺癌的临床数据及基因表达谱,采用Cox回归分析构建预后风险评估模型。结果: GEPIA2和THPA数据库结果显示,与非前列腺癌组织相比,AP1S1在前列腺癌组织中表达显著升高(P<0.05),qPCR实验结果进一步证实在前列腺癌组织中AP1S1 mRNA表达水平高于非前列腺癌组织(P<0.01)。生存分析结果表明,AP1S1高表达组的前列腺癌患者的DFS明显缩短(P=0.005),而OS无显著差异,且发现T分期、Gleason评分和AP1S1基因表达是前列腺癌患者生化复发的独立预后影响因素。GO和KEGG富集分析结果显示,AP1S1基因在细胞膜和肌动蛋白细胞骨架的组织构建、调控蛋白质稳定和分解、胞质分裂等相关信号通路中显著富集。结论: AP1S1在前列腺癌组织中呈高表达,并且与患者的不良预后相关,有可能作为新的生物标志物和治疗靶点。

Objective: Adaptor related protein complex 1 subunit sigma 1(AP1S1) is a protein-coding gene involved in encoding and assembling the adaptor protein complex. It plays a crucial role in regulating intracellular and extracellular transmembrane transport mechanisms and can affect the progression of various diseases. However, the role of AP1S1 in prostate cancer remains unclear. This study aims to explore the potential impact of AP1S1 on the occurrence and development of prostate cancer. Methods: The expression level of AP1S1 in prostate cancer and its relationship with overall survival(OS) and disease-free survival(DFS) were analyzed using GEPIA2, THPA, and TCGA databases. Additionally, 12 cases of prostate cancer and 12 cases of non-prostate cancer tissues were collected from Meizhou People's Hospital, and qPCR experiments were conducted to further verify the expression of AP1S1 in prostate cancer. Metascape tool was used for GO and KEGG enrichment analyses to explore the potential molecular mechanism of AP1S1 gene. R software was used to analyze the clinical data and gene expression profiles of prostate cancer in the TCGA database, and Cox regression analysis was performed to construct a prognostic risk assessment model. Results: The results from GEPIA2 and THPA databases showed that compared with non-prostate cancer tissues, the expression of AP1S1 in prostate cancer tissues was significantly increased(P<0.05). The results of qPCR experiments further confirmed that the expression level of AP1S1 mRNA in prostate cancer tissues was higher than that in non-prostate cancer tissues(P<0.01). Survival analysis results indicated that the DFS of prostate cancer patients in the AP1S1 high-expression group was significantly shortened(P=0.005), while there was no significant difference in OS. It was also found that T stage, Gleason score, and AP1S1 gene expression were independent prognostic factors for biochemical recurrence in prostate cancer patients. GO and KEGG enrichment analysis results showed that the AP1S1 gene was significantly enriched in signaling pathways related to the organization and construction of cell membranes and actin cytoskeletons, regulation of protein stability and decomposition, and cytokinesis. Conclusion: AP1S1 is highly expressed in prostate cancer tissues and is associated with poor prognosis in patients, which may serve as a new biomarker and therapeutic targe.

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