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DD3上调对前列腺癌早期检测及预后的影响。

Effect of upregulation of DD3 on early detection and prognosis in prostate cancer.

作者信息

Wang Ke, Zhao Huishan, Wang Wenting, Zhu Yingqian, Zhang Xuebao, Ma Jiajia, Tan Haotian, Zhang Yulian, Lin Chunhua

机构信息

Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

出版信息

Transl Androl Urol. 2020 Aug;9(4):1550-1558. doi: 10.21037/tau-19-899.

DOI:10.21037/tau-19-899
PMID:32944517
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7475679/
Abstract

BACKGROUND

Expression of prostate cancer antigen 3 (PCA3 OR ) in the blood has been reported to be significantly higher in prostate cancer (PCa) than in benign prostate hyperplasia (BPH). To confirm whether DD3 expression is significantly different between PCa and BPH tissues, DD3 expression was tested in the blood both preoperatively and postoperatively and in the paired tissues of PCa patients.

METHODS

Expression levels of DD3 mRNA in the blood of patients who did not undergo surgery (PCa, n=102; BPH, n=53), those underwent surgery (preoperative, n=35; postoperative, n=35), and in PCa tissue specimens (tumor, n=41; adjacent normal, n=21) were determined by real-time quantitative PCR. Sensitivity and specificity for DD3 in PCa patients were validated by receiver operating characteristic (ROC) curve analysis.

RESULTS

Our data suggest that expression level of DD3 in blood samples was significantly higher in PCa patients than in BPH patients (P=0.005). Expression of DD3 mRNA was also significantly elevated in PCa tissues compared with adjacent normal tissues (P=0.013). The increase in DD3 expression in PCa patients was further validated using a dataset from The Cancer Genome Atlas (n=549). Postoperative DD3 expression decreased following surgical intervention (P<0.001). Moreover, low DD3 expression was associated with improved overall survival (OS). Using gene set enrichment analysis, DD3 expression was correlated with specific PCa target genes including carcinogenesis-related and cancer proliferation-related genes.

CONCLUSIONS

This study demonstrated that expression of was upregulated in blood and PCa tumor tissues and was associated with prognosis. The oncogenic role of was further validated in the TCGA database, indicating that is a potential therapeutic target for PCa. Furthermore, this study suggests that expression could be considered as a prognostic biomarker for PCa.

摘要

背景

据报道,前列腺癌抗原3(PCA3 OR)在血液中的表达在前列腺癌(PCa)患者中显著高于良性前列腺增生(BPH)患者。为了证实DD3在PCa和BPH组织中的表达是否存在显著差异,我们对PCa患者术前和术后的血液以及配对组织中的DD3表达进行了检测。

方法

通过实时定量PCR测定未接受手术的患者(PCa,n = 102;BPH,n = 53)、接受手术的患者(术前,n = 35;术后,n = 35)血液以及PCa组织标本(肿瘤,n = 41;相邻正常组织,n = 21)中DD3 mRNA的表达水平。通过受试者工作特征(ROC)曲线分析验证DD3在PCa患者中的敏感性和特异性。

结果

我们的数据表明,PCa患者血液样本中DD3的表达水平显著高于BPH患者(P = 0.005)。与相邻正常组织相比,PCa组织中DD3 mRNA的表达也显著升高(P = 0.013)。使用来自癌症基因组图谱(n = 549)的数据集进一步验证了PCa患者中DD3表达的增加。手术干预后,术后DD3表达下降(P < 0.001)。此外,低DD3表达与总体生存率(OS)的改善相关。使用基因集富集分析,DD3表达与特定的PCa靶基因相关,包括致癌相关基因和癌症增殖相关基因。

结论

本研究表明,DD3在血液和PCa肿瘤组织中的表达上调,且与预后相关。DD3的致癌作用在TCGA数据库中得到进一步验证,表明DD3是PCa的潜在治疗靶点。此外,本研究表明,DD3表达可被视为PCa的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/e2534b74880e/tau-09-04-1550-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/d86e11385eb4/tau-09-04-1550-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/b4af87196ecc/tau-09-04-1550-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/a286ed8548e2/tau-09-04-1550-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/98416f1129c0/tau-09-04-1550-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/e2534b74880e/tau-09-04-1550-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/d86e11385eb4/tau-09-04-1550-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/b4af87196ecc/tau-09-04-1550-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/a286ed8548e2/tau-09-04-1550-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/98416f1129c0/tau-09-04-1550-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/7475679/e2534b74880e/tau-09-04-1550-f5.jpg

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本文引用的文献

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The Epidemiology of Prostate Cancer.前列腺癌的流行病学。
Cold Spring Harb Perspect Med. 2018 Dec 3;8(12):a030361. doi: 10.1101/cshperspect.a030361.
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Prostate cancer: Predicting risk of metastasis after prostatectomy.前列腺癌:前列腺切除术后转移风险的预测
Nat Rev Urol. 2018 Mar;15(3):137. doi: 10.1038/nrurol.2017.228. Epub 2018 Jan 3.
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Diagnostic significance of urinary long non-coding PCA3 RNA in prostate cancer.尿长链非编码PCA3 RNA在前列腺癌中的诊断意义
Oncotarget. 2017 Apr 20;8(35):58577-58586. doi: 10.18632/oncotarget.17272. eCollection 2017 Aug 29.
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GRP78 Participates in PCA3-regulated Prostate Cancer Progression.葡萄糖调节蛋白78参与PCA3调控的前列腺癌进展。
Anticancer Res. 2017 Aug;37(8):4303-4310. doi: 10.21873/anticanres.11823.
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Urinary Biomarker Panel to Improve Accuracy in Predicting Prostate Biopsy Result in Chinese Men with PSA 4-10 ng/mL.用于提高预测 PSA 为 4 - 10 ng/mL 的中国男性前列腺活检结果准确性的尿液生物标志物组合
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Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions.基于血液和尿液的前列腺癌生物标志物:用于检测和治疗决策的新型生物标志物综述与比较
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study.全球、区域和国家癌症发病率、死亡率、生命损失年数、失能生存年数以及 32 种癌症组别的伤残调整生命年数,1990 年至 2015 年:全球疾病负担研究的系统分析。
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PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells.PCA3长链非编码RNA调节LNCaP前列腺癌细胞中关键癌症相关基因的表达。
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