Gene expression pathways of high grade localized prostate cancer

Ross, Ashley E.; Marchionni, Luigi; Vuica‐Ross, Milena; Cheadle, Chris; Fan, Jinshui; Berman, David M.; Schaeffer, Edward M.

doi:10.1002/pros.21373

Cited by 76 publications

(83 citation statements)

References 60 publications

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“…We applied Analysis of Functional Annotation (AFA), a gene set analysis approach, on differential gene expression data obtained from distinct comparisons and across different studies to identify biological processes and signaling pathways modulated by HDACis in PCa cells. 10,11,18,19,65 Overall, this methodology extends gene set analysis procedures, such as GSEA or parametric analysis of gene set enrichment (PAGE), by investigating biological processes enrichment over multiple experimental conditions as briefly summarized below. [12][13][14] FGS, recapitulating distinct and complementary biological concepts such as cellular signaling pathways, PPI networks, downstream transcriptional responses, gene expression regulatory networks orchestrated by transcription factors and microRNA targets, were retrieved in the form of gene lists from various publicly available databases (see Table S1 and http://luigimarchionni.…”

Section: Methodsmentioning

confidence: 99%

“…15 In the current study, we applied AFA, as previously described, to enable the interpretation of these results in the context of relevant cancer biology. 10,11,[18][19][20] To this end, we selected Functional Gene Sets (FGS) from distinct databases, recapitulating different and complementary biological concepts: (1) cellular signaling pathways from Pathway Commons, (2) PPI networks from the National Center for Biotechnology Information (NCBI) Entrez Gene database, (3) downstream transcriptional responses, and (4) gene expression regulatory networks orchestrated by transcription factors and microRNA targets. These collections included, among others, the Human Protein Reference Database (HPRD), GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), the Molecular Signature Database (MSigDB), the Pathway Commons and NCBI Entrez Gene databases.…”

Section: Analysis Of Functional Annotation (Afa) After Treatment Withmentioning

confidence: 99%

“…S7-S16). 10,18,34 We also compared and validated AFA results identifying the biological themes and processes which were consistently differentially expressed across the data sets, treatment conditions, and data points analyzed (Figs. S17-S19).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

et al. 2013

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histone deacetylases (hDacs) have emerged as important targets for cancer treatment. hDac-inhibitors (hDacis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (cTcL).To improve the clinical benefit of hDacis in solid tumors, combination strategies with hDacis could be employed. In this study, we applied analysis of Functional annotation (aFa) to provide a comprehensive list of genes and pathways affected upon hDaci-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing aFa on gene expression data from prostate cancer cell lines DU-145 (an hDaci-sensitive cell line) and pc3 (a relatively hDaci-resistant cell line) treated with hDacis valproic acid or vorinostat, we identified biological processes that are affected by hDacis and are therefore potential treatment targets for combination therapy. Our analysis revealed that hDac-inhibition resulted among others in upregulation of major histocompatibility complex (Mhc) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by aFa on publicly available data sets from hDaci-treated prostate cancer cells. In total, we analyzed 375 microarrays with hDaci treated and non-treated (control) prostate cancer cells. all results from this extensive analysis are provided as an online research source (available at the journal's website and at http:// luigimarchionni.org/hDacIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after hDac-inhibition, and to identify novel potential combination strategies with hDacis for the treatment of prostate cancer patients. Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

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Section: Methodsmentioning

confidence: 99%

Section: Analysis Of Functional Annotation (Afa) After Treatment Withmentioning

confidence: 99%

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Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

et al. 2013

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“…In contrast, SPARCL1 gene expression was not significantly lost in benign prostatic hyperplasia or PIN (Fig. S6 D and E) (27,28,37) (Oncomine). Interestingly, gene-profiling data from the same cohorts showed that RHOC gene expression did not correlate with prostate cancer grade (Fig.…”

Section: Sparcl1 Expression Inversely Correlates With Prostate Cancermentioning

confidence: 95%

“…Interestingly, gene-profiling data from the same cohorts showed that RHOC gene expression did not correlate with prostate cancer grade (Fig. S6 F and G) (27,28), suggesting that alterations in RHOC activity as opposed to expression levels, mediate RHOCinduced metastatic progression (38).…”

Section: Sparcl1 Expression Inversely Correlates With Prostate Cancermentioning

confidence: 98%

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Hurley¹,

Marchionni²,

Simons³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.Hevin | synaptic cleft 1 | urogenital sinus | extracellular matrix P rostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in United States men. Controversy currently exists over the best treatment strategy for men with high-risk disease (clinical stage ≥T2c, Gleason score 8-10 or prostate-specific antigen > 20 ng/mL) because 56-65% of these men recur after definitive local therapy (1-5). This finding highlights the need for a better understanding of the biologic determinants driving disease progression for both prognostic and therapeutic development.We and others have recently illustrated that pathways essential for prostate organogenesis are reactivated in prostate cancer (6, 7). During organogenesis, androgens induce epithelialmesenchymal interactions in the urogenital sinus (UGS) and drive its differentiation into a prostate (8). We examined early prostate organogenesis shortly after initial androgen exposure, when urogenital sinus epithelia (UGE) migrate and invade into the surrounding mesenchyme and determined that the genes defining this developmental stage were similarly regulated in the transition between low-and high-grade prostate cancers (6). Among these genes, SPARCL1 (SPARC-like 1/Hevin/SC1), a member of the secreted protein, acidic and rich in cysteine (SPARC) family of matricellular proteins, was down-regulated specifically during embryoni...

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Active Surveillance for Low‐Risk Prostate Cancer

Klotz

2017

Management of Urologic Cancer

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Active surveillance for localized prostate cancer entails initial expectant management rather than immediate therapy, with "curative-intent" treatment deferred until there is evidence that the patient is at increased risk for disease progression. This is a response to the clearly documented risks of over diagnosis and overtreatment of low-risk prostate cancer, which in most cases poses little or no threat to the patient. It is based upon the prolonged natural history of prostate cancer and is an attempt to balance the risks and side effects of overtreatment against the possibility of disease progression and a lost opportunity for cure. Low-risk prostate cancer is more accurately viewed as one of multiple risk factors for the presence of higher grade prostate cancer. Like atypical small acinar proliferation, (ASAP), it may be managed with close follow up but without radical intervention, unless there is clear evidence of more aggressive disease.

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Gene expression pathways of high grade localized prostate cancer

Cited by 76 publications

References 60 publications

Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome

Active Surveillance for Low‐Risk Prostate Cancer

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