Clinical Utility and Biologic Implications of Phosphatase and Tensin Homolog (PTEN) and ETS-related Gene (ERG) in Prostate Cancer

Ullman, David; Dorn, David; Rais‐Bahrami, Soroush; Gordetsky, Jennifer B.

doi:10.1016/j.urology.2017.11.022

Cited by 16 publications

(11 citation statements)

References 90 publications

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“…Studies with murine models have suggested the existence of synergy between PTEN loss and ERG contributing to the oncogenesis of PCa (3,30), but in humans, this association is still a matter of debate. In a cohort of RP, Yoshimoto et al showed that PTEN deletion with the simultaneous presence of TMPRSS2-ERG abnormalities was associated with shorter time to biochemical recurrence of PCa (26).…”

Section: Discussionmentioning

confidence: 99%

“…Although Gleason score system, serum prostate-specific antigen (PSA), and clinical and pathological tumor stage are established tools for grading PCa, they are not capable of distinguishing men with high risk disease from the indolent majority. As a result, patients on active surveillance may lose the correct timing for treatment or suffer from unnecessary side effects of overtreatment (3). To overcome these issues, a lot of approaches are being explored, such as molecular biomarkers aiming to give information about the tumor biology and help predict the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Morais

Gurgel

Teixeira³

et al. 2019

Braz J Med Biol Res

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PTEN is the most commonly inactivated tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes. ERG rearrangement is a genomic alteration frequently found in PCa and its prognostic significance has yielded mixed results. Although the association of PTEN and ERG biomarkers has potential impact on clinical outcomes, studies examining the two genes simultaneously are scarce in Brazilian populations. In this study, we retrospectively examined the relationship between ERG expression and PTEN loss in 119 surgically treated prostate cancer patients from Northeastern Brazil through immunohistochemical analysis. ERG expression was found in 41.0% (48/117) of cases and the loss of PTEN detected in 38.1% (40/105) of samples. ERG-positive cases were significantly associated with lower prostate weight; ERG negatively correlated with Gleason score above 6. The lack of associations for PTEN loss alone in this cohort is counter to the literature, which shows that PTEN loss is usually associated with more aggressive disease. The overlapping of the two biomarkers revealed that samples with positive ERG expression without PTEN loss were associated with lower Gleason and lower Grade group. This study contributes with the discussion about the development of the molecular profiling of prostate cancer. The further development of similar studies could help in stratifying specific risk groups, leading to a more personalized therapeutic decision for prostate cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Morais

Gurgel

Teixeira³

et al. 2019

Braz J Med Biol Res

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“…Phosphatase and tensin homolog (PTEN) is a common tumor suppressor gene which has been found in many tumor types (17,18). As reported, PTEN was also found to be involved in PC (19).…”

Section: Introductionmentioning

confidence: 83%

Silencing miRNA‑1297 suppresses the invasion and migration of prostate cancer cells via targeting modulation of PTEN and blocking of the AKT/ERK pathway

2021

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Phosphatase and tensin homolog (PTEN) loss is a major contributing factor of prostate cancer (PC). miRNA-1297 was reported to serve role in various cancer types; however, the potential roles of miRNA-1297 in PC had not been investigated. In the present study, tumor and adjacent tissues were collected from patients with PC. The gene expression level of miRNA-1297 was measured via polymerase chain reaction. Results indicated that the miRNA-1297 was overexpressed in tumor tissues from PC patients and in PC cell lines. miRNA-1297 also contributed toward the progression of PC. PTEN was confirmed as the direct target of miRNA-1297 and bound with miRNA-1297 via four binding sites. The miRNA-1297 level was negatively associated with the PTEN level. Silencing miRNA-1297 or overexpression of PTEN significantly inhibited the cell migration and invasion. In addition, the AKT/ERK pathway was also inhibited following silencing of miRNA-1297 or overexpression of PTEN. Taken together, the results indicated that silencing miRNA-1297 exerted inhibitory effects on the invasion and migration of PC cells via modulating PTEN and blocking of the AKT/ERK pathway. The results of the present study provided a novel strategy for treatment of prostate cancer cells.

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“…Hägglöf et al showed that TMPRSS2-ERG was associated with increased cancer-specific mortality compared to patients whose tumors lacked ERG staining ( 52 ). However, other studies have failed to show clinical significance ( 53 ). Assays screening for TMPRSS2-ERG have been shown in multiple studies to improve detection of PCa.…”

Section: Urinary Biomarkers For Pcamentioning

confidence: 99%

Urinary markers aiding in the detection and risk stratification of prostate cancer

Raja

Russell

George

2018

Transl. Androl. Urol.

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The purpose of this review is to highlight the role of existing and promising urinary biomarkers for the detection and prognostication of prostate cancer (PCa). A number of novel urinary biomarkers have been introduced into the clinical space, which in combination with clinical variables, have demonstrated an increased ability to select patients for biopsy and identify men at risk of harboring clinically significant PCa. Though a number of assays require further validation, initial data is promising and forthcoming results will ultimately determine their clinical utility and commercial availability. For the past 30 years, first-line screening for PCa has relied on measurement of serum prostate-specific antigen (PSA) levels and the results from a digital rectal exam (DRE). A large body of evidence from the last 3 decades indicates that these screening methods are problematic, and often inadequate for detecting clinically significant PCa. Extensive efforts have recently been made to identify and commercialize novel PCa biomarkers for more effective detection of PCa, either alone or in combination with current screening methods. This review article highlights problems with current screening standards, and discusses 6 urinary biomarker assays in terms of their ability to detect and risk-stratify PCa: prostate cancer antigen 3 (PCA3), TMPRSS2-ERG, second chromosome locus associated with prostate-1 (SChLAP1), ExoDx, SelectMDx, and Michigan Prostate Score (MiPS).

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Clinical Utility and Biologic Implications of Phosphatase and Tensin Homolog (PTEN) and ETS-related Gene (ERG) in Prostate Cancer

Cited by 16 publications

References 90 publications

Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Prevalence of ERG expression and PTEN loss in a Brazilian prostate cancer cohort

Silencing miRNA‑1297 suppresses the invasion and migration of prostate cancer cells via targeting modulation of PTEN and blocking of the AKT/ERK pathway

Urinary markers aiding in the detection and risk stratification of prostate cancer

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