Prognostic Value of
            <i>RASSF1</i>
            Promoter Methylation in Prostate Cancer

Daniūnaitė, Kristina; Jarmalaitė, Sonata; Kalinauskaite, Neringa; Petroška, Donatas; Laurinavičius, Arvydas; Lazutka, Juozas R.; Jankevičius, Feliksas

doi:10.1016/j.juro.2014.06.075

Cited by 49 publications

(55 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies have identified new potential tumor markers including methylation of PITX2 , HOXD3 , APC , TGFβ2 , RASSF1A , ANEP , PCDH10 , ZNF132 , TDRD1 , AOX1 , C1orf114 , GAS6 , HAPLN3 , KLF8 , MOB3B , CCND2 , PTGS2 , RARB , SRD5A2 and CYP11A1 , thus emerging as new predictors of BCR particularly in high-risk clinically localized disease. Also the level of methylation of HSPB1 , the gene encoding heat shock protein-27 [25], and Ras association (RalGDS/AF-6) domain family member 1 ( RASSF1 ) [26] associate to death in low Gleason score PCa.…”

Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

View full text Add to dashboard Cite

Purpose: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation profile of patients with prostate cancer (PCa) predicts biochemical recurrence (BCR) after radical prostatectomy (RP). Material and Methods: Genome-wide methylation analysis was performed using the GoldenGate Methylation Cancer Panel-I (Illumina, Inc.) on 10 normal prostate tissues and 58 tumor samples from patients treated by RP followed for prostate-specific antigen (PSA) failure (>0.4 ng/ml) and disease progression. Patients were classified on the basis of D'Amico criteria according to clinical staging, PSA at diagnosis and Gleason score after pathologist review. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Hierarchical clustering analysis was performed and relationships with outcome were investigated using log-rank analysis and Cox regression model. Results: We found 28 genes significantly hypermethylated in >20% of the tumors analyzed. Four clusters of patients were characterized by their DNA methylation profile, one at higher risk to develop BCR (p = 0.005). Multivariate analysis revealed patients in this cluster (HR 2.56), and high-risk patients (HR 4.34) according to D'Amico classification were independent predictors of BCR after prostatectomy. From the selected genes MT1A, ALOX12, GSTM2, APC, MYCL2 and RARB hypermethylation predicted BCR and GSTM2 (HR 3.78) and MYCL2 hypermethylation (HR 2.71) did so independently. Conclusion: Epigenetic silencing of GSTM2 and MYCL2 comprise novel molecular markers to predict BCR after surgery for medium- and high-risk localized PCa undergoing surgical treatment and hypermethylation of these genes could be incorporated to the clinical and pathological factors defining the patient at higher risk of PSA failure after prostatectomy. The limitation of the study is that no independent validation cohort is analysed.

show abstract

Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

View full text Add to dashboard Cite

show abstract

“…Phosphorylation β loss of function in prostate cancer [119], CCL: overexpression inhibits cell proliferation and promote apoptosis in HepG2 cells [87] Mouse double KO: cholangiocarcinoma [46,101], HCC [120] Decreased mRNA level in tumour associated with node metastasis [121], mouse double KO: crypt dysplasia, colon adenoma [46,78,120] RASSF1, RASSF1A TSG: promoter hypermethylation and decrease expression in cancer: thyroid [122], oesophageal [123], prostate [124], colorectal, breast [125] TSG; promoter hypermethylation and decrease expression in CRC [126,127] SAV1, Salvador TSG: LOH and downregulation in renal cell carcinoma [128], no gene mutation in stomach, liver and lung cancer [129] CCL: overexpression induces apoptosis in MCF-7 cells [130] No gene mutation in CRC [129] LATS1 TSG: decrease expression in cancer: glioma [131], NSLC [132], sarcoma [133] and astrocytoma [134]. CCL: LATS1 degradation inhibits apoptosis in MCF10A cells [135] TSG: promoter hypermethylation and mRNA decrease in CRC [86] LATS2 TSG: decrease expression in: malignant mesothelioma (and LOH) [136], NSLC (no mutation found) [137] and astrocytoma [134] OG: overexpression in AML [138], nosopharyngeal carcinoma [139] TSG: downregulation in CRC [87] …”

Section: Stk4 Mst1 and Stk3 Mst2mentioning

confidence: 99%

The Hippo pathway in colorectal cancer

Wierzbicki

Rybarczyk

2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one the most frequently diagnosed neoplastic diseases worldwide. Currently, aside from traditional chemotherapy, advanced CRCs are treated with modern drugs targeting cellular components such as epithelial growth factor receptor (EGFR). Since up to 70% of metastasized CRCs are drug resistant, the description of recent progress in cellular homeostasis regulation may shed new light on the development of new molecular targets in cancer treatment. The Hippo pathway has recently become subject of intense investigations since it plays a crucial role in cell proliferation, differentiation, apoptosis and tumourigenesis. Components of the Hippo pathway are deregulated in various human malignancies, and expression levels of its major signal transducers were proposed as prognostic factors in colorectal cancer. In this review we focused on recent data regarding Hippo pathway, its up-stream signals and down-stream effectors. Hippo negatively regulates its major effectors, YAP1 and TAZ kinases, which act as transcriptional co-activators inducing expression of genes involved not only in tissue repair and proliferation but are also oncoproteins involved in tumour development and progression. The deregulation of Hippo pathway components was found in many malignancies. The interactions between Hippo and Wnt/b-catenin signalling, crucial in the maintenance of cell homeostasis, have been described in relation to the control of intestinal stem cell proliferation and CRC development. The recently discovered positive feedback loop between activated YAP1 and increased EGFR/KRAS signalling found in oesophageal, ovarian and hepatocellular cancer has been related to the CRC progression and resistance to EGFR inhibitors during CRC therapy.

show abstract

“…This alteration has been detected in many studies [25, 28, 34, 38], although some have reported controversial results [27, 29, 36]. Cho, NY et al [26].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis

Dou

Zhou

Fan

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Retinoic acid receptor beta (RAR beta) is a retinoic acid receptor gene that has been shown to play key roles during multiple cancer processes, including cell proliferation, apoptosis, migration and invasion. Numerous studies have found that methylation of the RAR beta promoter contributed to the occurrence and development of malignant tumors. However, the connection between RAR beta promoter methylation and prostate cancer (PCa) remains unknown. This meta-analysis evaluated the clinical significance of RAR beta promoter methylation in PCa. Materials and Methods: We searched all published records relevant to RAR beta and PCa in a series of databases, including PubMed, Embase, Cochrane Library, ISI Web of Science and CNKI. The rates of RAR beta promoter methylation in the PCa and control groups (including benign prostatic hyperplasia and normal prostate tissues) were summarized. In addition, we evaluated the source region of available samples and the methods used to detect methylation. To compare the incidence and variation in RAR beta promoter methylation in PCa and non-PCa tissues, the odds ratio (OR) and 95% confidence interval (CI) were calculated accordingly. All the data were analyzed with the statistical software STATA 12.0. Results: Based on the inclusion and exclusion criteria, 15 articles assessing 1,339 samples were further analyzed. These data showed that the RAR beta promoter methylation rates in PCa tissues were significantly higher than the rates in the non-PCa group (OR=21.65, 95% CI: 9.27-50.57). Subgroup analysis according to the source region of samples showed that heterogeneity in Asia was small (I²=0.0%, P=0.430). Additional subgroup analysis based on the method used to detect RAR beta promoter methylation showed that the heterogeneity detected by MSP (methylation-specific PCR) was relatively small (I²=11.3%, P=0.343). Conclusion: Although studies reported different rates for RAR beta promoter methylation in PCa tissues, the total analysis demonstrated that RAR beta promoter methylation may be correlated with PCa carcinogenesis and that the RAR beta gene is particularly susceptible. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic utility of RAR beta promoter methylation in PCa.

show abstract

Prognostic Value of RASSF1 Promoter Methylation in Prostate Cancer

Abstract: Hypermethylation of RASSF1 in cancerous tissue and urine from patients with prostate cancer correlated with biochemical recurrence after radical prostatectomy. The prognostic potential of this biomarker deserves further investigation.

Cited by 49 publications

References 21 publications

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

The Hippo pathway in colorectal cancer

Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis

Contact Info

Product

Resources

About