CDC20 和 PTTG1 是转移性前列腺癌的重要生物标志物和潜在治疗靶点。
CDC20 and PTTG1 are Important Biomarkers and Potential Therapeutic Targets for Metastatic Prostate Cancer.
机构信息
Department of Urology, The First Hospital of Qinhuangdao, No. 258 of Cultural North Road, Haigang District, Qinhuangdao, 066000, China.
Department of Pediatrics, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, China.
出版信息
Adv Ther. 2021 Jun;38(6):2973-2989. doi: 10.1007/s12325-021-01729-3. Epub 2021 Apr 21.
INTRODUCTION
Metastatic prostate cancer (mPCa) is responsible for most prostate cancer (PCa) deaths worldwide. The present study aims to explore the molecular differences between mPCa and PCa.
METHODS
The authors downloaded GSE6752, GSE6919, and GSE32269 from the Gene Expression Omnibus and employed integrated analysis to identify differentially expressed genes (DEGs) between mPCa and PCa. Functional and pathway-enrichment analyses were performed, and a protein-protein interaction (PPI) network and modules were constructed. Clinical mPCa specimens were collected to verify the results by performing RT-qPCR. The Cancer Genome Atlas database was used to conduct a survival analysis, and an immunohistochemical assay was performed. The invasion ability of PCa cells was verified by Transwell assay.
RESULTS
One-hundred six consistently DEGs were found in mPCa compared with PCa. DEGs significantly enriched the positive regulation of cell proliferation, cell division, and cell adhesion in small cell lung cancer and PCa. Cell division, nucleoplasm, and cell cycle were selected from the PPI network, and the top 10 hub genes were selected. CDC20 and PTTG1 with genetic alterations were significantly associated with poorer disease-free survival. Immunohistochemical assay results showed that the expression levels of CDC20 and PTTG1 in mPCa were higher than those in PCa. The results of the migration assay indicated that CDC20 and PTTG1 could enhance the migration ability of PCa cells.
CONCLUSION
The present study revealed that CDC20 and PTTG1 contribute more to migration, progression, and poorer prognoses in mPCa compared with PCa. CDC20 and PTTG1 could represent therapeutic targets in mPCa medical research and clinical studies.
简介
转移性前列腺癌（mPCa）是导致全球大多数前列腺癌（PCa）死亡的主要原因。本研究旨在探讨 mPCa 和 PCa 之间的分子差异。
方法
作者从基因表达综合数据库中下载了 GSE6752、GSE6919 和 GSE32269，通过综合分析鉴定 mPCa 和 PCa 之间差异表达的基因（DEGs）。进行功能和途径富集分析，并构建蛋白质-蛋白质相互作用（PPI）网络和模块。收集临床 mPCa 标本，通过 RT-qPCR 验证结果。使用癌症基因组图谱数据库进行生存分析，并进行免疫组织化学检测。通过 Transwell 检测验证 PCa 细胞的侵袭能力。
结果
与 PCa 相比，mPCa 中发现了 106 个一致的 DEGs。DEGs 显著富集了小细胞肺癌和 PCa 中细胞增殖、细胞分裂和细胞黏附的正调控。从 PPI 网络中选择了细胞分裂、核质和细胞周期，并选择了前 10 个枢纽基因。具有遗传改变的 CDC20 和 PTTG1 与无病生存率较差显著相关。免疫组织化学检测结果显示，mPCa 中 CDC20 和 PTTG1 的表达水平高于 PCa。迁移试验结果表明，CDC20 和 PTTG1 可增强 PCa 细胞的迁移能力。
结论
本研究表明，与 PCa 相比，CDC20 和 PTTG1 对 mPCa 的迁移、进展和预后较差的贡献更大。CDC20 和 PTTG1 可能成为 mPCa 医学研究和临床研究中的治疗靶点。
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