mRNA Expression of S100A8 as a Prognostic Marker for Progression of Non-Muscle-Invasive Bladder Cancer

Ha, Yun‐Sok; Kim, Min-Ju; Yoon, Hyung-Yoon; Hj, Kang; Kim, Yong‐June; Yun, Seok‐Joong; Lee, Sang Cheol; Kim, Wun-Jae

doi:10.4111/kju.2010.51.1.15

Cited by 17 publications

(18 citation statements)

References 25 publications

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“…They are involved in several cellular processes including transcription, proliferation and differentiation 49. In the recent study, the mRNA level of S100A8 could be the prognostic marker of bladder cancer 50. In our result, the mRNA levels of two genes were down‐regulated when LSD1 was silenced which was consistent with the previous report 35.…”

Section: Discussionsupporting

confidence: 91%

Cryptotanshinone down‐regulates androgen receptor signaling by modulating lysine‐specific demethylase 1 function

Hsieh

Huang

et al. 2011

Intl Journal of Cancer

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Development and progression of prostate cancer are intimately associated with androgen receptor (AR) signaling. The emergence of hormone-refractory prostate cancer and consequent failure of conventional androgen deprivation therapies make it necessary to bypass hormonal resistance by targeting the same signaling pathway at new intervention points. In our study, we showed that cryptotanshinone inhibited the growth of AR-positive prostate cancer cells, suggesting that cryptotanshinone affected AR function. Cryptotanshinone also profoundly inhibited the transcriptional activity of AR and suppressed the expression of several AR-target genes at the mRNA and the protein levels. At the molecular level, cryptotanshinone disrupted the interaction between AR and lysine-specific demethylase 1 (LSD1), and inhibited the complex of AR and LSD1 to the promoter of AR target genes without affecting the protein degradation and translocation of AR. Cryptotanshinone increased the monomethyl and di-methylation of Histone H3 lysine 9 (H3K9), a repressive histone marker which is demethylated and activated by LSD1. These data suggest that cryptotanshinone functions via inhibition of LSD1, a protein that promotes AR-dependent transcriptional activity via derepression of H3K9. In summary, we describe a novel mechanism whereby cryptotanshinone downregulates AR signaling via functional inhibition of LSD1-mediated demethylation of H3K9 and represses the transcriptional activity of AR. Our data suggest that cryptotanshinone can be developed as a potential therapeutic agent for prostate cancer.

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Section: Discussionsupporting

confidence: 91%

Cryptotanshinone down‐regulates androgen receptor signaling by modulating lysine‐specific demethylase 1 function

Hsieh

Huang

et al. 2011

Intl Journal of Cancer

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“…In Korea, BC is the second most common urological malignancy and is about five times more common in male as compared to female individuals (2). Patients diagnosed with non-muscle invasive bladder cancers (NMIBC) may have indolent, albeit recurrent, disease.…”

Section: Introductionmentioning

confidence: 99%

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Jeong

Cho

et al. 2011

Oncology Letters

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Abstract.The clinical grades and staging methods currently employed for bladder cancer (BC) are inadequate for assessing treatment outcomes for non-muscle invasive bladder cancer (NMIBC). We have developed a clinically applicable quantitative real-time PCR (qPCR) gene signature to predict the progression of NMIBC. Three genes not previously described for BC were selected from our published progression-related gene classifier data set. Data were drawn from a previous study population and from new cases. Primary NMIBC tissue specimens (n=193) were analyzed by qPCR. Risk scores were then used to rank specimens into high-and low-risk signature groups based on their gene expression. The Kaplan-Meier method and a multivariate Cox regression model were used to identify the prognostic value of the three-gene signature for both recurrence and progression. The Kaplan-Meier estimates revealed significant differences in time-to-recurrence and progression between low-and high-risk signatures (log-rank test, p=0.011 and p<0.001, respectively). The multivariate Cox regression analysis showed that the three-gene risk signature is an independent predictor of bladder tumor progression (hazard ratio, 4.268; 95% CI, 1.542-11.814; p=0.005). In conclusion, our three-gene signature was found to be closely associated with progression among patients with NMIBC. IntroductionBladder cancer (BC), the incidence and mortality of which increases directly with age, is a heterogeneous disease that affects approxi mately 68,000 people in the United States annually (1). In Korea, BC is the second most common urological malignancy and is about five times more common in male as compared to female individuals (2). Patients diagnosed with non-muscle invasive bladder cancers (NMIBC) may have indolent, albeit recurrent, disease. However, NMIBC patients are required to receive frequent cystourethroscopy, which is inconvenient for patients. Additionally, they may experience progression to muscle invasive bladder cancer (MIBC), which potentially has a narrow window-of-cure and requires aggressive treatment (3). Therefore, predicting the course of the disease is of great value to both patients and urologists, in order for adequate management of NMIBC to occur. For example, early radical cystectomy has a superior 5-year survival rate compared to bladder-sparing surgery (4). The development of accurate and reliable biological markers would be useful for assessing aggressiveness and for predicting the prognosis of NMIBC.Previously, we undertook a microarray analysis of specimens derived from 103 primary NMIBC patients and identified an eight-gene progression-related gene classifier (5). Although there have been numerous attempts to establish prognostic markers for NMIBC (3,(6)(7)(8)

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“…This is sustained by the facts that S100A9 is secreted by epithelial and other cell types to modulate inflammatory reactions as well as to promote cancer proliferation and metastasis. Two recent studies propose S100A8 and S100A9 gene expression as prognostic value for bladder cancer (Minami et al, 2010;Ha et al, 2010). By proteomic analysis of pre-and postoperative sera from bladder cancer patients S100A8 and S100A9 were identified as tumor-associated proteins (Minami et al, 2010).…”

Section: Bladder Cancersmentioning

confidence: 99%

“…In addition, the expression of both proteins S100A8/A9 was correlated with recurrence-free survival. In another study it was evaluated whether S100A8 is a prognostic value for non-muscle-invasive bladder cancer (NMIBC) (Ha et al, 2010). S100A8 expression was evaluated in a total of 103 primary NMIBC samples by quantitative PCR.…”

Section: Bladder Cancersmentioning

confidence: 99%

S100A9 (S100 calcium binding protein A9)

Kerkhoff¹,

Ghavami²

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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mRNA Expression of S100A8 as a Prognostic Marker for Progression of Non-Muscle-Invasive Bladder Cancer

Cited by 17 publications

References 25 publications

Cryptotanshinone down‐regulates androgen receptor signaling by modulating lysine‐specific demethylase 1 function

Cryptotanshinone down‐regulates androgen receptor signaling by modulating lysine‐specific demethylase 1 function

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

S100A9 (S100 calcium binding protein A9)

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