scholarly journals Frequent Methylation of RASSF1 and RARB in Urine Sediments From Patients with Early Stage Prostate Cancer

Medicina ◽  
2011 ◽  
Vol 47 (3) ◽  
pp. 20
Author(s):  
Kristina Daniūnaitė ◽  
Artūras Berezniakovas ◽  
Feliksas Jankevičius ◽  
Arvydas Laurinavičius ◽  
Juozas Lazutka ◽  
...  

Background. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. Material and Methods. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. Results. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). Conclusions. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa.

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xindong Zhang ◽  
Lin Gao ◽  
Zhi-Ping Liu ◽  
Songwei Jia ◽  
Luonan Chen

As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data.


2021 ◽  
Author(s):  
Eva Hulstaert ◽  
Annelien Morlion ◽  
Justine Nuytens ◽  
Giovanni Ponti ◽  
Monia Maccaferri ◽  
...  

A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.


The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1705-1714 ◽  
Author(s):  
Palak G. Patel ◽  
Thomas Wessel ◽  
Atsunari Kawashima ◽  
John B. A. Okello ◽  
Tamara Jamaspishvili ◽  
...  

2010 ◽  
Author(s):  
Masatoshi Watanabe ◽  
Yoshifumi Hirokawa ◽  
Hiroyoshi Suzuki ◽  
Tomohiko Ichikawa ◽  
Takahiko Katoh ◽  
...  

2006 ◽  
Vol 13 (2) ◽  
pp. 357-377 ◽  
Author(s):  
Antoinette S Perry ◽  
Ruth Foley ◽  
Karen Woodson ◽  
Mark Lawler

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor β2 (RARβ2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.


2013 ◽  
Author(s):  
Po-Hsien J. Huang ◽  
Wolfgang Göring ◽  
Thomas Hielscher ◽  
Dieter Weichenhan ◽  
Wolfgang A. Schulz ◽  
...  

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 357 ◽  
Author(s):  
Sandra Nunes ◽  
Catarina Moreira-Barbosa ◽  
Sofia Salta ◽  
Susana Palma de Sousa ◽  
Inês Pousa ◽  
...  

Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARβ2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers’ diagnostic performance was also evaluated. Results: A “PanCancer” panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a “CancerType” panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA’s methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects’ triage, increasing compliance and cost-effectiveness.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 55-55
Author(s):  
Scott Michael Gilbert ◽  
Rodney Dunn ◽  
Jeffrey Scott Montgomery ◽  
David Miller ◽  
Ted A. Skolarus ◽  
...  

55 Background: Prostate cancer accounts for greater than 200,000 cases each year. Although cancer control is generally favorable with treatment, side effects are common. Among men treated with surgery, nerve-sparing prostatectomy is associated with lower rates of incontinence and erectile dysfunction. Seminal vesicle sparing (SVS) may further limit damage to the neurovascular tissue surrounding the prostate. Although some surgeons practice SVS, evidence supporting its use is lacking. We implemented a randomized control trial to determine if SVS is associated with better functional outcomes compared to non-SVS prostatectomy. Methods: 140 men with early-stage (T1c/T2N0M0, Gleason score <= 7) prostate cancer and adequate erectile function (IIEF >= 21) were enrolled in the Seminal Vesicle Sparing Prostatectomy Trial (NCT01825642) and randomized to either SVS or non-SVS prostatectomy between 2006 and 2011. The Expanded Prostate Cancer Index Composite (EPIC) was used to assess quality of life outcomes following surgery. Results: 71 and 69 men were enrolled in the SVS and non-SVS arms, respectively. The predominant surgical approach was robotic assisted prostatectomy (>97% in both arms). Men in the SVS arm were slightly younger (56 vs 58 years, p = 0.02); however, there were no significant differences in other clinical or demographic factors. There were no cases of seminal vesicle invasion. PSA recurrence was noted in 3 patients (1 in SVS group and 2 in non-SVS group). At 12 months postoperatively, sexual (76 vs 75) and urinary incontinence (92 vs 94) scores were similar among SVS and non-SVS patients (both p > 0.2). Conclusions: Recovery of urinary and sexual function was common among men undergoing SVS or non-SVS prostatectomy. SVS did not negatively impact cancer control, but was not associated with enhanced recovery of sexual or urinary function, perhaps due to the high level of recovery of the control arm. Clinical trial information: NCT01825642. [Table: see text]


2020 ◽  
Vol 16 (3) ◽  
pp. 425-440
Author(s):  
Lingling Li ◽  
Bing Han ◽  
Ying Wang ◽  
Hai Shi ◽  
Jing Zhao ◽  
...  

Background: Cancer is one of most dangerous diseases that seriously threaten human health, while tumor biomarkers provide important information for clinical diagnosis and treatment of cancers. Given the low abundance of tumor biomarkers in the bodily fluids at the early stage of cancers, it is particularly important to develop bio sensing methods for accurate measurement of tumor biomarkers with high sensitivity. Objective: Nowadays, gold nanoparticles (AuNPs) that have remarkable physical and chemical properties are extensively used in the design of biosensing strategies. In this context, we mainly review the research progress of AuNPs-based biosensing methods for tumor-related biomedical applications in bodily fluids in recent years. Results: Optical, electrochemical and mass spectrometric biosensing methods using AuNPs are widely used for excellent performances in the assay of tumor biomarkers. Conclusion: The existing methods demonstrate high clinical value, while challenges and expectation of biosensing method in tumor-related biomedical application are also discussed.


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