ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Kelly, Gregory M.; Kong, Yink Heay; Dobi, Albert; Srivastava, Shiv; Sesterhenn, Isabell A.; Rajadurai, Pathmanathan; Tan, Hui Meng; Tan, Shyh‐Han; Cheong, Sok Ching

doi:10.3892/mco.2014.418

Cited by 7 publications

(4 citation statements)

References 47 publications

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“…Furthermore, intra-tumor differences in ERG alterations may lead to expression of ERG variants, which could be further exacerbated by inter-tumor heterogeneity [98, 99]. Although fusion of the AR regulated TMPRSS2 promoter to ETS related gene ( ERG ) that results in ERG overexpression [25, 26] is a common event in CA prostate cancer patients (50–70%), it is less frequent among AA and other ethnic groups [100–103]. In these populations, the detection of ERG may no longer be significant as prognostic biomarker for progression to BCR.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifiesERGas the strongest independent predictor of recurrence

et al. 2019

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Background: As a major cause of morbidity and mortality among men, prostate cancer is a heterogenous disease, with a vast heterogeneity in the biology of the disease and in clinical outcome. While it often runs an indolent course, local progression or metastasis may eventually develop, even among patients considered “low risk” at diagnosis. Therefore, biomarkers that can discriminate aggressive from indolent disease at an early stage would greatly benefit patients. We hypothesized that tissue specimens from early stage prostate cancers may harbor predictive signatures for disease progression.Methods: We used a cohort of radical prostatectomy patients with longitudinal follow-up, who had tumors with low grade and stage that revealed no signs of future disease progression at surgery. During the follow-up period, some patients either remained indolent (non-BCR) or progressed to biochemical recurrence (BCR). Total RNA was extracted from tumor, and adjacent normal epithelium of formalin-fixed-paraffin-embedded (FFPE) specimens. Differential gene expression in tumors, and in tumor versus normal tissues between BCR and non-BCR patients were analyzed by NanoString using a customized CodeSet of 151 probes.Results: After controlling for false discovery rates, we identified a panel of eight genes (ERG, GGT1, HDAC1, KLK2, MYO6, PLA2G7, BICD1 and CACNAID) that distinguished BCR from non-BCR patients. We found a clear association of ERG expression with non-BCR, which was further corroborated by quantitative RT-PCR and immunohistochemistry assays.Conclusions: Our results identified ERG as the strongest predictor for BCR and showed that potential prognostic prostate cancer biomarkers can be identified from FFPE tumor specimens.

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Section: Discussionmentioning

confidence: 99%

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifiesERGas the strongest independent predictor of recurrence

et al. 2019

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“…Alternatively, when there is information available regarding the expression status of genes and/or proteins, we have the option of selecting specific candidate protein as a substrate for exploring the detection of AAbs. In the context of CaP, we utilized the latter approach, as overexpression of ERG has been previously reported from analysis of patient specimens [ 52 , 56 , 60 , 62 , 66 ]. Despite the documentation of the TMPRSS2-ERG gene fusion in about 50% prostate CA cancer patients, there is no information available regarding the presence of AAbs against ERG protein.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, Caucasian Americans (CA) have shown to harbor this gene fusion in around 50 % of CaP cases, while African Americans (AA) have shown a lower level of roughly 20-30% of CaP patients. Regarding other racial/ethnic groups, ERG prevalence has been shown at variable levels [ 9 , 64 - 66 ]. As a result, there have been efforts to develop two new tests for the detection of CaP using this gene fusion.…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies against oncogenic ERG protein in prostate cancer: potential use in diagnosis and prognosis in a panel with C-MYC, AMACR and HERV-K Gag

Rastogi

Tan

et al. 2017

Genes Cancer

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Overdiagnosis and overtreatment of prostate cancer (CaP) is attributable to widespread reliance on PSA screening in the US. This has prompted us and others to search for improved biomarkers for CaP, to facilitate early detection and disease stratification. In this regard, autoantibodies (AAbs) against tumor antigens could serve as potential candidates for diagnosis and prognosis of CaP. Towards this, our goals were: i) To investigate whether AAbs against ERG oncoprotein (overexpressed in 25-50% of Caucasian American and African American CaP) are present in the sera of CaP patients; ii) To evaluate an AAb panel to enhance CaP detection. The results using an enzyme-linked immunosorbent assay (ELISA) showed that anti-ERG AAbs are present in a significantly higher proportion in the sera of CaP patients compared to healthy controls (p = 0.0001). Furthermore, a panel of AAbs against ERG, AMACR and human endogenous retrovirus-K Gag successfully differentiated CaP patient sera from healthy controls (AUC = 0.791). These results demonstrate for the first time that anti-ERG AAbs are present in the sera of CaP patients. In addition, the data also suggest that AAbs against ERG together with AMACR and HERV-K Gag may be a useful panel of biomarkers for diagnosis and prognosis of CaP.

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“…All of these studies indicate that there is differential gene expression between AA and EA PCa. The TMPRSS2/ERG fusion gene is much less frequent in AA PCa based on studies of DNA, RNA and protein (8–16). Elevated SPINK1 expression appears to be more common in AA PCa (8,9,17–19).…”

Section: Introductionmentioning

confidence: 99%

RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression

Wang

Zhang

et al. 2017

Cancer Research

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African American (AA) men exhibit a relatively high incidence and mortality due to prostate cancer (PCa) even after adjustment for socioeconomic factors, but the biological basis for this disparity is unclear. Here we identify a novel region on chromosome 4p16.3 that is lost selectively in AA PCa. The negative regulator of G-protein signaling RGS12 was defined as the target of 4p16.3 deletions, although it has not been implicated previously as a tumor suppressor gene. RGS12 transcript levels were relatively reduced in AA PCa and PCa cell lines showed decreased RGS12 expression relative to benign prostate epithelial cells. Notably, RGS12 exhibited potent tumor suppressor activity in PCa and prostate epithelial cell lines in vitro and in vivo. We found that RGS12 expression correlated negatively with the oncogene MNX1 and regulated its expression in vitro and in vivo. Further, MNX1 was regulated by AKT activity and RGS12 expression decreased total and activated AKT levels. Our findings identify RGS12 is a candidate tumor suppressor gene in AA PCa which acts by decreasing expression of AKT and MNX1, establishing a novel oncogenic axis in this disparate disease setting.

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ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Cited by 7 publications

References 47 publications

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifiesERGas the strongest independent predictor of recurrence

Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifiesERGas the strongest independent predictor of recurrence

Autoantibodies against oncogenic ERG protein in prostate cancer: potential use in diagnosis and prognosis in a panel with C-MYC, AMACR and HERV-K Gag

RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression

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