Generation of a prognostic cancer stem-like gene expression signature in men undergoing radical prostatectomy for localized prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4563-4563
Author(s):  
Adrian Stuart Fairey ◽  
Dongyun Yang ◽  
Susan G. Groshen ◽  
David I. Quinn ◽  
Philip Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Wnt Signaling Pathway ◽  
Gene Expression Signature ◽  
Disease Recurrence ◽  
Localized Prostate Cancer ◽  
Mrna Levels ◽  
Expression Signature

4563 Background: Novel biomarkers are needed to predict recurrence after radical prostatectomy for localized prostate cancer. Recent data suggest that cancer stem-like cells (CSC) are present in prostate tumors, and the CSC phenotype has been associated with an aggressive cancer phenotype. We investigated whether tumor mRNA levels of genes typically expressed by CSC are associated with disease recurrence. Methods: Clinically annotated prostatectomy specimens (FFPE) were used for this nested case-control study. Samples represented men who underwent radical prostatectomy and either experienced a recurrence (PSA or clinical; n=152) or no recurrence (controls; n=124) with minimum 5-year follow-up. Men were excluded if they received neoadjuvant hormone therapy. Cases and controls were frequency matched based on D’Amico risk group. Laser capture microdissection with mRNA extraction and quantitative RT-PCR were used to quantify the expression of 12 candidate CSC-associated genes (ALDH1A1, Axin2, Bmi1, CD133, CD44a, CTNNB1/β-catenin, ITGA2/integrin α2, NANOG, Nkx3-1, Notch1, OCT 4, TACSTD2/Trop2). Univariable and multivariable analyses were conducted to measure associations with recurrence. Results: mRNA data were evaluable for 241 of 276 patients. Univariate Wilcoxon analysis showed that 4 genes (Axin2, p<0.001; CD44a, p=0.036; OCT 4, p=0.017; TACSTD2, p=0.008) were expressed at low levels in tumors of patients whose disease recurred. Recursive partitioning analysis identified 3 genes significantly predictive of disease recurrence (Axin2, NANOG, CTNNB1), with cutpoints yielding odds ratios (OR) of 8.5 (Axin2low/NANOGhigh; n=94, 95%CI 3.7-19.2) and 5.1 (Axin2low/NANOGvery high/CTNNB1low; n=26, 95%CI 1.7-14.8). Conclusions: We identified a novel CSC-associated 3 gene expression signature with the potential to predict recurrence after radical prostatectomy. Axin2 is known to interact with CTNNB1/β-catenin in the Wnt signaling pathway, which in turn has been shown to regulate expression of NANOG, a key protein that mediates pluripotency. In vitro experiments and an independent cohort validation study are planned based on these novel findings.

scholarly journals Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort

Oncotarget ◽  
2017 ◽  
Vol 8 (26) ◽  
pp. 43035-43047 ◽  
Author(s):  
Min A. Jhun ◽  
Milan S. Geybels ◽  
Jonathan L. Wright ◽  
Suzanne Kolb ◽  
Craig April ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Gene Expression Signature ◽  
Cancer Outcomes ◽  
Expression Signature

Novel Gene Expression Signature Predictive of Clinical Recurrence After Radical Prostatectomy in Early Stage Prostate Cancer Patients

The Prostate ◽  
2016 ◽  
Vol 76 (14) ◽  
pp. 1239-1256 ◽  
Author(s):  
Ahva Shahabi ◽  
Juan Pablo Lewinger ◽  
Jie Ren ◽  
Craig April ◽  
Andy E. Sherrod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Early Stage ◽  
Gene Expression Signature ◽  
Clinical Recurrence ◽  
Expression Signature ◽  
Novel Gene

730 THE ATORVASTATIN TARGET SCD1 IDENTIFIED WITHIN THE GENE EXPRESSION SIGNATURE OF HIGH BMI PROSTATE CANCER PATIENTS

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Patrick Parker ◽  
Shashwat Sharad ◽  
Anjali Srivastava ◽  
Suma Ravulapalli ◽  
Yongmei Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Patients ◽  
Gene Expression Signature ◽  
Expression Signature ◽  
High Bmi

A gene expression signature to predict high-grade prostate cancer response to oxaliplatin.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 150-150
Author(s):  
Philippe Pourquier ◽  
Stephane Puyo ◽  
Pierre Richaud ◽  
Jacques Robert ◽  
Nadine Houede
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Trials ◽  
Cell Lines ◽  
Gene Expression Signature ◽  
Chemotherapeutic Agents ◽  
Low Grade ◽  
Gleason Grade ◽  
High Grade ◽  
Expression Signature

150 Background: Prostate cancer (PCa) is one of the leading causes of death from cancer in men. High Gleason grade prostate cancers are characterized by aggressive tumors with poorly differentiated cells and a high metastatic potential. They are often refractory to chemical castration but still treated with hormone therapy to which docetaxel or cabazitaxel are added when they become resistant to the anti-androgen. Despite many clinical trials with other chemotherapeutic agents, response rates remain low. Moreover, none of these trials took into account the tumor grade. Methods: We used an in silico approach to screen for drug candidates that could be used as an alternative to taxanes, based on a 86 genes signature which could distinguish between low-grade and high-grade tumors. We extracted from the NCI60 panel databases the expression profiles of the 86 genes across 60 human tumor cell lines and the corresponding in vitro cytotoxicity data of 152 drugs and looked for correlation between their expression level and cell sensitivity to each of these drugs. Results: Among the 86 genes, we identified 9 genes (PCCB, SHMT2, DPM1, RHOT2, RPL13, CD59, EIF4AI, CDKN2C, JUN) for which expression levels across the 60 cell lines was significantly correlated (p< 0.05) to oxaliplatin but not to cisplatin sensitivity. This signature was validated at the functional level since repression of each of these genes conferred a significant change in the sensitivity of PCa cell lines to oxaliplatin but not cisplatin. Conclusions: Our results provide a proof of concept that gene expression signature specific from high grade PCa could be used for the identification of alternative therapies to taxanes. They could also be used to select patients for further clinical trials and as predictive markers of response to these drugs, which represents a further step forward towards personalized therapy of PCa.

Discovery and validation of a 30-gene expression signature to identify prostate cancer patients who are candidates for active surveillance.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 10-10
Author(s):  
Travis Gerke ◽  
Svitlana Tyekucheva ◽  
Kathryn Penney ◽  
Christopher Sweeney ◽  
Rosina Lis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Active Surveillance ◽  
Control Sample ◽  
Gene Expression Signature ◽  
Health Study ◽  
Validation Data ◽  
Expression Signature ◽  
Indolent Disease

10 Background: Considerable attention has been devoted to the search for biomarkers of aggressive prostate cancer. While many promising markers have been proposed, it is often unclear whether their ability to risk classify is adequate to reduce overtreatment of indolent cancers. We present and validate a gene expression signature that is highly specific for indolent disease and that, when combined with Gleason, improves upon the prognostic power of Gleason alone. Methods: A 30-gene signature of indolent disease was derived from a case-control sample of men (n=254) from the Health Professionals Follow-Up Study (HPFS) who were followed prospectively from cancer diagnosis for a median of 13.7 years. Cases were defined as men with prostate cancer who experienced a metastatic event or died of cancer during follow-up, while indolent controls survived at least 8 years without metastases. Whole-transcriptome gene expression was quantified from archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens acquired at prostatectomy. Genes were selected by a novel analytic strategy that maximizes a partial area under the curve (pAUC) to accurately identify indolent tumors. We validated the signature in two independent cohorts: the Physicians’ Health Study (PHS; n=150) and a Swedish Watchful Waiting cohort (WW; n=253) with respective median follow-up times of 14.4 and 9.0 years. Results: When compared to a model with Gleason alone, application of the signature to both validation data sets significantly improved prognostic accuracy as measured by pAUC (p=0.003 in PHS and p<0.001 in WW). Performance was particularly strong among men diagnosed with Gleason 7, where unit standard deviation increases in the signature score were associated with odds ratios of indolence of 5.24 (95% CI 2.21-15.75; p<0.001) and 2.37 (95% CI 1.45-4.19; p=0.001) in the PHS and WW cohorts, respectively. Conclusions: We present a signature of indolent prostate cancer that adds prognostic information beyond Gleason and has the potential to guide men to active surveillance and avoid overtreatment. Validation across both treated and untreated cohorts supports the discovery of a robust signature.

scholarly journals A 12-Gene Expression Signature Is Associated with Aggressive Histological in Prostate Cancer

2012 ◽  
Vol 181 (5) ◽  
pp. 1585-1594 ◽  
Author(s):  
Laia Agell ◽  
Silvia Hernández ◽  
Lara Nonell ◽  
Marta Lorenzo ◽  
Eulàlia Puigdecanet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Gene Expression Signature ◽  
Expression Signature

scholarly journals Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

2007 ◽  
Vol 104 (18) ◽  
pp. 7564-7569 ◽  
Author(s):  
Lao H. Saal ◽  
Peter Johansson ◽  
Karolina Holm ◽  
Sofia K. Gruvberger-Saal ◽  
Qing-Bai She ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Signature ◽  
Pi3k Pathway ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Pathway Activity ◽  
Pten Loss ◽  
Expression Signature ◽  
Cancer Management ◽  
Pathway Activation

Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.

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