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Abstract：
BACKGROUND: This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of prostate cancer (PCa).
METHODS: Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using \"pRRophetic\". Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy.
RESULTS: The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy.
CONCLUSIONS: In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.
METHODS: Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using \"pRRophetic\". Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy.
RESULTS: The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy.
CONCLUSIONS: In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.
摘要：
背景：本文试图阐明空泡蛋白分选相关蛋白72同源物（VPS72）在前列腺癌（PCa）进展中的作用和机制。
方法：前列腺癌患者的临床信息和基因表达谱来自癌症基因组图谱（TCGA）。研究了VPS72在PCa中的表达和VPS72影响PCa进展的潜在机制。接下来,我们进行了COX回归分析，以确定PCa的独立预后因素，并构造了一个列线图。使用“pRophetic”可以预期化疗药物的敏感性。随后，体外试验验证VPS72对PCa细胞增殖的影响，迁移和抗雄激素治疗的敏感性。
结果：与正常组织相比，PCa组织中VPS72的表达明显更高。VPS72高表达与不良预后和不良临床病理因素之间存在显着相关性。基于VPS72表达式构建的列线图模型具有良好的预测性能。根据GSEA，VPS72相关基因在NF-kB通路中富集，PCa中细胞因子-细胞因子受体相互作用和趋化因子信号通路。尽管低VPS72表达的PCa更适合化疗药物，我们的体外实验表明，VPS72敲低显著降低了PCa细胞的迁移，扩散,以及对抗雄激素治疗的抗性。
结论：总之，我们的研究结果表明，VPS72可能在PCa的恶性进展中起关键作用，其表达水平可作为PCa预后的可能生物标志物。
方法：前列腺癌患者的临床信息和基因表达谱来自癌症基因组图谱（TCGA）。研究了VPS72在PCa中的表达和VPS72影响PCa进展的潜在机制。接下来,我们进行了COX回归分析，以确定PCa的独立预后因素，并构造了一个列线图。使用“pRophetic”可以预期化疗药物的敏感性。随后，体外试验验证VPS72对PCa细胞增殖的影响，迁移和抗雄激素治疗的敏感性。
结果：与正常组织相比，PCa组织中VPS72的表达明显更高。VPS72高表达与不良预后和不良临床病理因素之间存在显着相关性。基于VPS72表达式构建的列线图模型具有良好的预测性能。根据GSEA，VPS72相关基因在NF-kB通路中富集，PCa中细胞因子-细胞因子受体相互作用和趋化因子信号通路。尽管低VPS72表达的PCa更适合化疗药物，我们的体外实验表明，VPS72敲低显著降低了PCa细胞的迁移，扩散,以及对抗雄激素治疗的抗性。
结论：总之，我们的研究结果表明，VPS72可能在PCa的恶性进展中起关键作用，其表达水平可作为PCa预后的可能生物标志物。
