Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

doi:10.1038/srep25776

Cited by 87 publications

(70 citation statements)

References 58 publications

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“…The AUC of the optimal model with PCA3 for cancer detection was 0.75 compared with an AUC of 0.71 for the optimal model without PCA3. A meta‐analysis of 46 clinical trials including 12 265 men who underwent PCA3 testing showed that the sensitivity and specificity for the detection of prostate cancer were 65% and 73%, respectively, although this meta‐analysis did not separate men with a first biopsy and a repeat biopsy . A PCA3‐based nomogram for the prediction of prostate cancer and high‐grade prostate cancer at the time of initial biopsy was also developed using the information of age, serum PSA, DRE prostate volume and PCA3 level .…”

Section: Rna In Urinementioning

confidence: 99%

Urinary biomarkers of prostate cancer

2018

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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.

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Section: Rna In Urinementioning

confidence: 99%

Urinary biomarkers of prostate cancer

2018

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“…Maternally expressed gene 3 (MEG3) is decreased in prostate cancer tissues, and upregulation of MEG3 inhibits intrinsic cell survival pathway and induces cell-cycle arrest in G 0 -G 1 phase (35). Prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors and described as a novel biomarker of prostate cancer (36,37). The association between lncRNA GAS5 and the progression of various cancers has been demonstrated in previous studies.…”

Section: Discussionmentioning

confidence: 94%

LncRNA GAS5 Inhibits Cellular Proliferation by Targeting P27Kip1

Luo

Liu

Huang

et al. 2017

Molecular Cancer Research

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Recent studies have demonstrated that long noncoding RNAs (lncRNA) have important roles in cancer biology, and that the downregulation of lncRNA growth arrest-specific transcript 5 (GAS5) has been reported in a variety of human cancers. However, its role in prostate cancer is largely unknown. This study aims to investigate the biological role and underlying mechanism of GAS5 on proliferation in prostate cancer. The results demonstrate that GAS5 expression is significantly decreased in prostate cancer cells compared with prostate epithelial cells. Ectopic expression of GAS5 inhibited cell proliferation and induced a cell-cycle arrest in G-G phase, whereas GAS5 knockdown promoted the G-S phase transition. Subsequent analysis demonstrated that P27, a known regulator of cell cycle, was positively regulated by GAS5 and upregulation of GAS5 increased its promoter activity. E2F1, an important transcription factor, was shown to bind directly to and activate the P27 promoter. In addition, GAS5 interacted with E2F1 and enhanced the binding of E2F1 to the P27 promoter. Collectively, these findings determine that GAS5 functions as a tumor suppressor in prostate cancer development and progression via targeting P27 This study reveals a molecular pathway involving lncRNA GAS5/E2F1/P27 which regulates cell proliferation and could be a potential therapeutic target in prostate cancer. .

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“…Additional details are available at www.gen-probe.com. PCA3 has a pooled sensitivity of 65% and specificity of 73%, based on a meta-analysis of 46 clinical trials (5). …”

Section: Molecular Diagnostic Tools For Prostate Cancer: Current Non-mentioning

confidence: 99%

Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management

et al. 2018

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Prostate cancer is a complex disease, with multiple subtypes and clinical presentations. Much progress has been made in recent years to understand the underlying genetic basis that drives prostate cancer. Such mechanistic information is useful for development of novel therapeutic targets, to identify biomarkers for early detection or to distinguish between aggressive and indolent disease, and to predict treatment outcome. Multiple tests have become available in recent years to address these clinical needs for prostate cancer. We describe several of these assays, summarizing test details, performance characteristics, and acknowledging their limitations. There is a pressing unmet need for novel biomarkers that can demonstrate improvement in these areas. We introduce one such candidate biomarker, RAD9, describe its functions in the DNA damage response, and detail why it can potentially fill this void. RAD9 has multiple roles in prostate carcinogenesis, making it potentially useful as a clinical tool for men with prostate cancer. RAD9 was originally identified as a radioresistance gene, and subsequent investigations revealed several key functions in the response of cells to DNA damage, including involvement in cell cycle checkpoint control, at least five DNA repair pathways, and apoptosis. Further studies indicated aberrant overexpression in approximately 45% of prostate tumors, with a strong correlation between RAD9 abundance and cancer stage. A causal relationship between RAD9 and prostate cancer was first demonstrated using a mouse model, where tumorigenicity of human prostate cancer cells after subcutaneous injection into nude mice was diminished when RNA interference was used to reduce the normally high levels of the protein. In addition to activity needed for the initial development of tumors, cell culture studies indicated roles for RAD9 in promoting prostate cancer progression by controlling cell migration and invasion through regulation of ITGB1 protein levels, and anoikis resistance by modulating AKT activation. Furthermore, RAD9 enhances the resistance of human prostate cancer cells to radiation in part by regulating ITGB1 protein abundance. RAD9 binds androgen receptor and inhibits androgen-induced androgen receptor's activity as a transcription factor. Moreover, RAD9 also acts as a gene-specific transcription factor, through binding p53 consensus sequences at target gene promoters, and this likely contributes to its oncogenic activity. Given these diverse and extensive activities, RAD9 plays important roles in the initiation and progression of prostate cancer and can potentially serve as a valuable biomarker useful in the management of patients with this disease.

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Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

Cited by 87 publications

References 58 publications

Urinary biomarkers of prostate cancer

Urinary biomarkers of prostate cancer

LncRNA GAS5 Inhibits Cellular Proliferation by Targeting P27Kip1

Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management

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