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前列腺癌的尿液生物标志物

Urinary biomarkers of prostate cancer.

作者信息

Fujita Kazutoshi, Nonomura Norio

机构信息

Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

出版信息

Int J Urol. 2018 Sep;25(9):770-779. doi: 10.1111/iju.13734. Epub 2018 Aug 21.

Abstract

The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200 nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

摘要

开发更具特异性的前列腺癌和/或高危前列腺癌生物标志物很有必要,因为前列腺特异性抗原检测在前列腺癌检测方面缺乏特异性,可能导致不必要的前列腺活检。尿液是开发前列腺癌新生物标志物的一个有前景的来源。源自前列腺癌细胞的生物标志物会释放到前列腺液中,然后进入尿液。对前列腺进行操作后的尿液富含前列腺癌生物标志物,包括前列腺癌细胞、DNA、RNA、蛋白质和其他小分子。尿前列腺癌抗原3检测是美国食品药品监督管理局批准的首个基于RNA的尿液标志物,有助于在重复活检时检测前列腺癌。SelectMDx检测基于前列腺按摩后尿液中DLX1和HOXC6的信使RNA检测,有助于在前列腺活检时检测高危前列腺癌。外泌体是直径为30 - 200纳米的细胞外囊泡,由各种类型的细胞分泌。源自前列腺癌的尿液外泌体也含有前列腺癌特异性的RNA和蛋白质(如PCA3和TMPRSS2-ERG),可能是发现新型生物标志物的有前景的来源。ExoDx Prostate检测是一种基于检测尿液外泌体中三个基因(PCA3、ERG和SPDEF)的商业检测方法。综合分析(微阵列、质谱和下一代测序)的进展已导致发现了几种尿液生物标志物。非侵入性尿液标志物有助于决定是否进行前列腺活检或设计治疗策略。

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