基于生物信息学和体外实验鉴定前列腺癌骨转移相关基因和潜在治疗靶点。
Identification of prostate cancer bone metastasis related genes and potential therapy targets by bioinformatics and in vitro experiments.
机构信息
Department of Urology I, The Third Affiliated Hospital of Kunming Medical University (Peking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, Cancer Center of Yunnan Province), Kunming, Yunnan, China.
Department of Urology II, The second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
出版信息
J Cell Mol Med. 2024 Aug;28(15):e18511. doi: 10.1111/jcmm.18511.
The aetiology of bone metastasis in prostate cancer (PCa) remains unclear. This study aims to identify hub genes involved in this process. We utilized machine learning, GO, KEGG, GSEA, Single-cell analysis, ROC methods to identify hub genes for bone metastasis in PCa using the TCGA and GEO databases. Potential drugs targeting these genes were identified. We validated these results using 16 specimens from patients with PCa and analysed the relationship between the hub genes and clinical features. The impact of APOC1 on PCa was assessed through in vitro experiments. Seven hub genes with AUC values of 0.727-0.926 were identified. APOC1, CFH, NUSAP1 and LGALS1 were highly expressed in bone metastasis tissues, while NR4A2, ADRB2 and ZNF331 exhibited an opposite trend. Immunohistochemistry further confirmed these results. The oxidative phosphorylation pathway was significantly enriched by the identified genes. Aflatoxin B1, benzo(a)pyrene, cyclosporine were identified as potential drugs. APOC1 expression was correlated with clinical features of PCa metastasis. Silencing APOC1 significantly inhibited PCa cell proliferation, clonality, and migration in vitro. This study identified 7 hub genes that potentially facilitate bone metastasis in PCa through mitochondrial metabolic reprogramming. APOC1 emerged as a promising therapeutic target and prognostic marker for PCa with bone metastasis.
前列腺癌（PCa）骨转移的病因尚不清楚。本研究旨在确定参与这一过程的关键基因。我们利用机器学习、GO、KEGG、GSEA、单细胞分析、ROC 方法，使用 TCGA 和 GEO 数据库鉴定 PCa 骨转移的关键基因。鉴定了针对这些基因的潜在药物。我们使用来自 16 名 PCa 患者的 16 个标本验证了这些结果，并分析了关键基因与临床特征之间的关系。通过体外实验评估了 APOC1 对 PCa 的影响。确定了 7 个 AUC 值为 0.727-0.926 的关键基因。APOC1、CFH、NUSAP1 和 LGALS1 在骨转移组织中高表达，而 NR4A2、ADRB2 和 ZNF331 则表现出相反的趋势。免疫组织化学进一步证实了这些结果。确定的基因显著富集了氧化磷酸化途径。鉴定出黄曲霉毒素 B1、苯并（a）芘、环孢素作为潜在药物。APOC1 的表达与 PCa 转移的临床特征相关。体外沉默 APOC1 可显著抑制 PCa 细胞的增殖、克隆性和迁移。本研究确定了 7 个关键基因，它们通过线粒体代谢重编程促进 PCa 骨转移。APOC1 是一种很有前途的治疗靶点和具有骨转移的 PCa 的预后标志物。
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