Development of a Multiplexed Urine Assay for Prostate Cancer Diagnosis

Vener, Tatiana; Derecho, Carlo; Baden, Jonathan; Wang, Haiying; Rajpurohit, Yashoda; Skelton, Joanne; Mehrotra, Jyoti; Varde, Shobha; Chowdary, Dondapati; Stallings, Walt; Leibovich, Bradley C.; Robin, H; Pelzer, Alexandre; Schäfer, Georg; Auprich, Marco; Mannweiler, Sebastian; Amersdorfer, Peter; Mazumder, Abhijit

doi:10.1373/clinchem.2007.094912

Cited by 52 publications

(40 citation statements)

References 27 publications

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“…In prostate cancer, expression of RARβ2 is decreased or lost and this loss of expression is found associated with methylation in the promoter region 76. Methylation of RARβ2 in the promoter region has been frequently detected in PIN (low level), primary tumors, and hormone-refractory tumors (high level), but not in BPH and normal prostate 117–120…”

Section: Hypermethylated Genes In Prostate Cancermentioning

confidence: 99%

Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples

Ahmed

2010

Biomark�Cancer

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Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

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Section: Hypermethylated Genes In Prostate Cancermentioning

confidence: 99%

Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples

Ahmed

2010

Biomark�Cancer

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“…The use of voided urine samples in an attempt to diagnosis PCa is gaining widespread attention. For example, investigators are using RT-PCR to identify the prostate cancer antigen 3 (PCA-3) [12] and glutathione S-transferase P1 12 gene [13] in voided urine samples. Particularly, the sensitivity and specificity of PCA-3 have been reported to be 54% and 74%, respectively, for the entire cohort and 53% and 71%, respectively, for PSA within 4–10 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid

et al. 2014

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BackgroundPast attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples.MethodsOne hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence).ResultsOf the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX–PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX–PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score.ConclusionsTo our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX–PPD for PCa detection.

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“…A new molecular biomarker is still required for the screening of prostate cancer. In this section, studies of methylation analyses of urinary DNA for the early detection of prostate cancer are reviewed (Table 5 and Table S5) [105,106,107,108,109,110,111,112,113,114]. …”

Section: Use Of Bodily Fluids For Cancer Detectionmentioning

confidence: 99%

“…The panel of four genes ( p16 , ARF , MGMT , and GSTP1 ) could discriminate prostate cancer with a sensitivity and specificity of 87% and 100%, respectively. In 2008, Venar et al [114] conducted a multicenter prospective study for patients with PSA levels higher than 2.5 ng/mL. Urinary samples were collected after the DRE procedure.…”

Section: Use Of Bodily Fluids For Cancer Detectionmentioning

confidence: 99%

Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

Yokoi

Yamashita

Watanabe

2017

IJMS

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Epigenetic alterations by promoter DNA hypermethylation and gene silencing in cancer have been reported over the past few decades. DNA hypermethylation has great potential to serve as a screening marker, a prognostic marker, and a therapeutic surveillance marker in cancer clinics. Some bodily fluids, such as stool or urine, were obtainable without any invasion to the body. Thus, such bodily fluids were suitable samples for high throughput cancer surveillance. Analyzing the methylation status of bodily fluids around the cancer tissue may, additionally, lead to the early detection of cancer, because several genes in cancer tissues are reported to be cancer-specifically hypermethylated. Recently, several studies that analyzed the methylation status of DNA in bodily fluids were conducted, and some of the results have potential for future development and further clinical use. In fact, a stool DNA test was approved by the U.S. Food and Drug Administration (FDA) for the screening of colorectal cancer. Another promising methylation marker has been identified in various bodily fluids for several cancers. We reviewed studies that analyzed DNA methylation in bodily fluids as a less-invasive cancer screening.

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Development of a Multiplexed Urine Assay for Prostate Cancer Diagnosis

Abstract: BACKGROUND: Several studies have demonstrated the value of DNA methylation in urine-based assays for prostate cancer diagnosis. However, a multicenter validation with a clinical prototype has not been published.

Cited by 52 publications

References 27 publications

Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples

Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples

Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid

Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

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