Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China; Department of Botany and Plant Sciences, University of California, Riverside 92507, USA.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China; Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, China.
Int J Biol Macromol. 2018 Oct 15;118(Pt A):599-609. doi: 10.1016/j.ijbiomac.2018.06.005. Epub 2018 Jun 3.
Although dCTP pyrophosphatase 1 (DCTPP1) has been reported to be associated with poor clinical outcomes in various cancers, whether it plays an important role in prostate cancer (PCa) remains unclear. In this study, an immunohistochemical assay showed the protein expression level of DCTPP1 was significantly higher in PCa tissues than in non-cancerous tissues. Moreover, DCTPP1 was upregulated at both protein and mRNA levels in the PCa tissues from high Gleason score patients versus low Gleason score patients. The analysis of The Cancer Genome Atlas RNA-seq data suggested that upregulation of DCTPP1 was inversely correlated with biochemical recurrence free survival and overall survival. The roles of DCTPP1 in tumor progression and autophagy were further validated through cells invasion, migration, apoptosis and proliferation assays in vitro, as well as EMT and autophagy assays in vivo. Advanced bioinformatics analysis identified the evidence supporting the promotional role of DCTPP1 in tumor progression associated with autophagy. We conclude that DCTPP1 may play an important role in PCa progression associated with high autophagy. Overexpression of DCTPP1 may server as a biomarker for predicting poor BCR-free survival and overall survival for PCa patients.
虽然 dCTP 焦磷酸酶 1（DCTPP1）已被报道与多种癌症的不良临床结局相关，但它是否在前列腺癌（PCa）中发挥重要作用仍不清楚。在这项研究中，免疫组织化学检测表明，DCTPP1 蛋白在前列腺癌组织中的表达水平明显高于非癌组织。此外，在高 Gleason 评分患者与低 Gleason 评分患者的前列腺癌组织中，DCTPP1 在蛋白和 mRNA 水平上均上调。对癌症基因组图谱 RNA-seq 数据的分析表明，DCTPP1 的上调与生化复发无进展生存和总生存呈负相关。通过体外细胞侵袭、迁移、凋亡和增殖试验以及体内 EMT 和自噬试验进一步验证了 DCTPP1 在肿瘤进展和自噬中的作用。先进的生物信息学分析为 DCTPP1 在与自噬相关的肿瘤进展中发挥促进作用提供了证据。我们得出结论，DCTPP1 可能在与高自噬相关的 PCa 进展中发挥重要作用。DCTPP1 的过表达可能可作为预测 PCa 患者生化无复发生存和总生存不良的生物标志物。
