Immunohistochemical staining of ERG and SOX9 as potential biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer

Song, Wan; Kwon, Ghee Young; Kim, Jeong Hoon; Lim, Ji Hyun; Jeon, Hwang Gyun; Seo, Seong Il; Jeon, Seong Soo; Choi, Han Yong; Jeong, Byong Chang; Lee, Hyun Moo

doi:10.18632/oncotarget.13407

Cited by 18 publications

(23 citation statements)

References 27 publications

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“…At the same time, some researchers have used high-throughput tissue gene chips to screen highly expressed SOX9 gene in PC patients. The above indicate that SOX9 gene has a certain correlation with the incidence of PC (17). In this study, siRNA was applied to silence SOX9 gene in PC-3 cell line, which manifested that the proliferation and migration abilities of PC-3 cells were significantly reduced.…”

Section: Discussionmentioning

confidence: 77%

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer

Song

Hua

et al. 2018

Oncol Lett

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Correlation of sex determining region Y-box (SOX)9 and NM23 genes with the incidence and prognosis of prostate cancer (PC) was investigated. SOX9-small interfering ribonucleic acid (siRNA) and NM23-siRNA were constructed and transfected into PC-3 cells. The expression levels of SOX9 and NM23 messenger RNAs (mRNAs) and proteins in PC-3 cells were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. MTT assay was adopted to examine the proliferation ability of the transfected cells, and Transwell assay was applied to detect the migration ability of the transfected cells. Sixty-three patients with PC and 56 patients with benign prostatic hyperplasia who were treated in Huadu District People's Hospital were enrolled. Correlation analyses were conducted for the relative expression levels of SOX9 and NM23 and the Gleason grade; and the survival curves of the patient SOX9/NM23 (S/N) Cq values were plotted. The proliferation and migration abilities of PC-3 cells were remarkably reduced after low expression of SOX9 (P<0.01), while those of PC-3 cells were significantly improved after low expression of NM23 (P<0.01). Compared with that in tissues of PC patients, the relative expression of SOX9 mRNA in patients with benign prostatic hyperplasia was obviously decreased (P<0.01), while that of NM23 mRNA was significantly elevated (P<0.01). The larger the S/N was, the shorter the patient's survival time would be (P<0.05). The low expression of SOX9 gene can significantly reduce the proliferation and migration abilities of PC cells, which is negatively associated with the incidence and prognosis of patients. The low expression of NM23 gene can markedly enhance the proliferation and migration abilities of PC cells, and it is positively related to the incidence and prognosis of patients.

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Section: Discussionmentioning

confidence: 77%

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer

Song

Hua

et al. 2018

Oncol Lett

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“…Only two articles were available for screening of ERG as biomarker. ERG positivity correlated with a lower PSA-PFS (3.2 months vs 7.4 months, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001) and OS (10.8 mos vs 21.4 mos, p < 0.001), thus indicating that ERG is potential biomarker for prediction to docetaxel treatment in mCRPC patients [ 42 ]. However, another study showed that ERG expression was not associated with risk of CRPC for predicting response to primary ADT in mCRPC patients [ 43 ] (Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Presence of CTC in patients after 3 months of initiation of ADT therapy was associated as a negative marker for early progression to CRPC [27]. Lesser explored biomarkers such as tyrosine phosphatase showed that higher levels predicted poorer OS and CSS in the two included studies [75,76] while patients with ERG positive values showed poorer outcomes of OS and PFS [42,43].…”

Section: Discussionmentioning

confidence: 97%

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

et al. 2020

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Background: Diagnosis of metastatic castrate resistant prostate cancer (mCRPC) with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment. There are a number of prognostic biomarkers for CRPC, but there are no validated predictive biomarkers to guide in clinical decision-making. Specific biomarkers are needed that enable to understand the natural history and complex biology of this heterogeneous malignancy, identify early response to treatment outcomes and to identify the population of men most likely to benefit from the treatment. In this systematic review, we discuss the existing literature for the role of biomarkers in CRPC and how they aid in the prognosis, treatment selection and survival outcomes. Methods: We performed a literature search on PubMed and EMBASE databases from January 2015 through February 2020 in accordance to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Articles were assessed to identify relevant observational studies and randomized controlled trials regarding biomarkers which aid in identifying progression to mCRPC as well as predictive biomarkers which help in treatment selection. Results: We identified 3640 number of hits of which 58 articles were found to be relevant. Here we addressed biomarkers in the context of prognosis, prediction and patient selection of therapy. These biomarkers were found to be effective as prognostic or predictive factors under variety of conditions. The higher levels for all these biomarkers were associated with shorter median OS and sometimes PFS. Lower amounts of biomarkers in serum or urine were associated with prolonged survival outcomes, longer time to CRPC development or CRPC progression and longer median follow-up irrespective of any therapy. Conclusion: We observed that the biomarkers included in our study predicted clinically relevant survival outcomes and treatment exposure. Though the current biomarkers are prognostic when measured prior to initiating treatment, not all are validated as predictive markers in post treatment setting. A greater understanding of biomarkers in CRPC is need of the hour for development of more personalized approach to maximize benefit and minimize harm in men with CRPC.

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“…Galletti et al have shown that ERG expression inhibits response to taxanes such as docetaxel in vitro and in mouse xenograft models. In addition, several groups have shown an inverse correlation between ERG expression and response to taxane treatment . These findings suggest that suppression of ERG expression may enhance responses to docetaxel treatment.…”

Section: Introductionmentioning

confidence: 86%

“…In addition, several groups have shown an inverse correlation between ERG expression and response to taxane treatment. [11][12][13] These findings suggest that suppression of ERG expression may enhance responses to docetaxel treatment.…”

mentioning

confidence: 86%

Targeting the TMPRSS2/ERG fusion mRNA using liposomal nanovectors enhances docetaxel treatment in prostate cancer

Shao

Kahraman

et al. 2019

The Prostate

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Background The TMPRSS2/ERG (TE) fusion gene is present in half of the prostate cancers (PCas). The TMPRSS2 and ERG junction of the fusion messenger RNA (mRNA) constitutes a cancer‐specific target. Although docetaxel‐based chemotherapy is the second line of therapy following development resistance to androgen ablation therapies, it is not curative. Therefore, the development of nontoxic novel monotherapies for targeting TE mRNA in PCa patients and for increasing the clinical efficacy of docetaxel treatment are needed. Methods We evaluated multiple approaches to enhance the delivery of TE small interfering RNA (siRNA) containing liposomes including PEGylation, topical treatment with nitroglycerin (NG) to increase permeability and retention, and three different PEG modifications: folate, RGD cyclic peptide, and a bFGF fibroblast growth factor receptor‐targeting peptide. The efficacy of the optimized TE siRNA liposome in combination with docetaxel was then evaluated in vivo with or without topical NG in vivo using a VCaP xenograft model. TE fusion protein knockdown in residual tumors was assessed using Western blotting and immunohistochemistry. Results In vivo therapeutic targeting of TE fusion gene by systemic delivery of RGD‐peptide‐coated liposomal siRNA nanovectors led to sustained target silencing, suppressed tumor growth in xenograft models and enhanced the efficacy of docetaxel chemotherapy. Simultaneous application of the vasodilator NG to the skin further increased tissue the delivery of siRNA and enhanced target knockdown. Conclusion TE‐targeted gene silencing therapy using liposomal nanovectors is a potential therapeutic strategy as a monotherapy and to enhance the efficacy of chemotherapy in patients with advanced PCa.

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Immunohistochemical staining of ERG and SOX9 as potential biomarkers of docetaxel response in patients with metastatic castration-resistant prostate cancer

Cited by 18 publications

References 27 publications

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

Targeting the TMPRSS2/ERG fusion mRNA using liposomal nanovectors enhances docetaxel treatment in prostate cancer

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