Prospero homeobox 1 promotes proliferation, migration, and invasion of osteosarcoma cells and its clinical significance

Osteosarcoma (OS) is the most common primary malignant bone tumor. Prospero homeobox 1 (PROX1) is a key transcription factor involved in some cancers, but the role of PROX1 in OS is unclear. This study aimed to explore the clinical and biology significance of PROX1 in OS. Fifty-four OS tissues and matched nontumor tissues were collected to explore the relationship between <i>PROX1</i> expression and clinical characteristics and prognosis. qRT-PCR and immunohistochemistry were used to investigate the expression patterns of PROX1 in OS tissues and cells. CCK-8, wound healing, and transwell assays were used to detect the effects of PROX1 on the proliferation, migration, and invasion of OS cells. Transcriptome sequencing, bioinformatics analysis and qRT-PCR were used to explore the regulatory network of PROX1. PROX1 was significantly higher in OS tissues and cells compared to normal tissues and cell lines. In OS patients, high expression of PROX1 was associated with Enneking stage (P &lt; 0.001) and M classification (P &lt; 0.001). High PROX1 expression predicted a poorer overall survival (P = 0.0047). Compared with untreated cells, OS cells overexpressing <i>PROX1</i> showed higher proliferation, migration, and invasion abilities, while knockdown of <i>PROX1</i> suppressed these abilities. The results of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the down regulated genes were mainly enriched in TNF signaling pathway, MAPK signaling pathway, and neuroactive ligand-receptor interaction. High <i>PROX1</i> expression was significantly associated with poor overall survival in OS patients. PROX1 may be a promising prognostic marker and therapeutic target for OS patients.

骨肉瘤（Osteosarcoma，OS）是最常见的原发性恶性骨肿瘤。Prospero同源框蛋白1（Prospero homeobox 1，PROX1）是参与多种癌症发生发展的关键转录因子，但其在骨肉瘤中的作用尚未明确。本研究旨在探讨PROX1在骨肉瘤中的临床及生物学意义。本研究收集了54份骨肉瘤组织及配对的正常对照组织，以探究*PROX1*的表达与临床特征及预后的关联；采用实时荧光定量聚合酶链反应（qRT-PCR）与免疫组织化学技术，检测PROX1在骨肉瘤组织及细胞中的表达模式；通过CCK-8实验、划痕愈合实验及Transwell实验，分析PROX1对骨肉瘤细胞增殖、迁移及侵袭能力的影响；并借助转录组测序、生物信息学分析及qRT-PCR，解析PROX1的调控网络。结果显示，相较于正常组织与细胞系，PROX1在骨肉瘤组织及细胞中的表达水平显著升高。在骨肉瘤患者中，PROX1高表达与Enneking分期（P < 0.001）及M分类（P < 0.001）显著相关；PROX1高表达提示患者总体生存期更短（P = 0.0047）。与未处理的对照细胞相比，过表达*PROX1*的骨肉瘤细胞增殖、迁移及侵袭能力显著增强，而敲低*PROX1*则可抑制上述生物学行为。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析结果显示，下调基因主要富集于TNF信号通路、MAPK信号通路及神经活性配体-受体相互作用通路。PROX1高表达与骨肉瘤患者较差的总体生存期显著相关，提示PROX1有望成为骨肉瘤患者潜在的预后标志物及治疗靶点。