Faculty Opinions recommendation of A molecular signature predictive of indolent prostate cancer.

Background. Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer death in men. Recent studies suggest the molecular signature was more effective than the clinical indicators for the prognostic prediction, but all of the known studies focused on a single RNA type. The present study was to develop a new prognostic signature by integrating long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) and evaluate its prognostic performance. Methods. The RNA expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus database (GSE17951, GSE7076, and GSE16560). The PCa-driven modules were identified by constructing a weighted gene coexpression network, the corresponding genes of which were overlapped with differentially expressed RNAs (DERs) screened by the MetaDE package. The optimal prognostic signature was screened using the least absolute shrinkage and selection operator analysis. The prognostic performance and functions of the combined prognostic signature was then assessed. Results. Twelve PCa-driven modules were identified using TCGA dataset and validated in the GSE17951 and GSE7076 datasets, and six of them were considered to be preserved. A total of 217 genes in these 6 modules were overlapped with 699 DERs, from which a nine-gene prognostic signature was identified (including 3 lncRNAs and 6 mRNAs), and the risk score of each patient was calculated. The overall survival was significantly shortened in patients having the risk score higher than the cut-off, which was demonstrated in TCGA (p=5.063E−03) dataset and validated in the GSE16560 (p=3.268E−02) dataset. The prediction accuracy of this risk score was higher than that of clinical indicators (the Gleason score and prostate-specific antigen) or the single RNA type, with the area under the receiver operator characteristic curve of 0.945. Besides, some new therapeutic targets and mechanisms (MAGI2-AS3-SPARC/GJA1/CYSLTR1, DLG5-AS1-DEFB1, and RHPN1-AS1-CDC45/ORC) were also revealed. Conclusion. The risk score system established in this study may provide a novel reliable method to identify PCa patients at a high risk of death.

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Nine-Gene Molecular Signature Is Not Associated with Prostate Cancer Death in a Watchful Waiting Cohort

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-07-0722 ◽

2008 ◽

Vol 17 (1) ◽

pp. 249-251 ◽

Cited By ~ 11

Author(s):

L. A. Mucci ◽

Y. Pawitan ◽

F. Demichelis ◽

K. Fall ◽

J. R. Stark ◽

...

Keyword(s):

Prostate Cancer ◽

Watchful Waiting ◽

Molecular Signature ◽

Cancer Death ◽

Prostate Cancer Death

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Molecular profiles of prostate cancer versus today’s diagnostic tools

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14659 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14659-14659

Author(s):

V. Vuaroqueaux ◽

P. Diener ◽

S. Eppenberger-Castori ◽

M. Labuhn ◽

C. Horica ◽

...

Keyword(s):

Prostate Cancer ◽

Target Genes ◽

Tnm Staging ◽

Molecular Signature ◽

Diagnostic Tools ◽

Molecular Profile ◽

Agglomerative Clustering ◽

Proliferation Markers ◽

Short Period ◽

Molecular Profiles

14659 Background: Tumor size, nodal status, the Gleason grading system and serum PSA values are today’s available prognostic tools of localized prostate cancer and the only help for adjuvant therapy. Based on the results of a feasibility study we continued the evaluation of the recently developed prognostic molecular signature. Methods: Of 60 CaP patients, who underwent primary prostatectomy in 2003 to 2005, fresh frozen samples of the tumor were asserved. The RNA extracted from cryocuts was tested. The quantitative RNA expression levels of 90 relevant genes involved in the different tumor hallmarks were simultaneously assessed. Results: Unsupervised agglomerative clustering of the obtained molecular profiles revealed different signatures. Correlations between these groups and the known TNM staging as well as Gleason scores were strongly present. Of interest was that all recurrences observed within this short period of time were found in a single cluster expressing higher levels of proliferation markers. Conclusions: The molecular profile of primary prostate cancer by quantitative RT-PCR is a powerful tool describing the biology of an individual tumor. Gene expression profiling can be precisely quantified and seems to be better reproducible than pathological judgments of the Gleason scores. Moreover, the gene panel is partially based on drug target genes and therefore of predictive value. Finally the method could be applied also in core biopsies. [Table: see text]

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Abstract 4351: Identification of molecular signature associated with the castration-resistant prostate cancer (CRPC) development by next-generation sequencing (NGS)-based transcriptomic profiling

10.1158/1538-7445.am2015-4351 ◽

2015 ◽

Author(s):

Seon-Kyu Kim ◽

Jeong-Hwan Kim ◽

Pildu Jeong ◽

Wun-Jae Kim ◽

Yong Sung Kim ◽

...

Keyword(s):

Prostate Cancer ◽

Next Generation Sequencing ◽

Molecular Signature ◽

Next Generation ◽

Castration Resistant Prostate Cancer ◽

Transcriptomic Profiling ◽

Castration Resistant ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

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Signalling pathways in prostate carcinogenesis: potentials for molecular-targeted therapy

Clinical Science ◽

10.1042/cs20080391 ◽

2009 ◽

Vol 117 (6) ◽

pp. 209-228 ◽

Cited By ~ 21

Author(s):

Alison K. Ramsay ◽

Hing Y. LEUNG

Keyword(s):

Prostate Cancer ◽

Drug Development ◽

Treatment Options ◽

Developed Countries ◽

Molecular Signature ◽

Signalling Pathways ◽

Resistant Disease ◽

Molecular Oncology ◽

Prostate Carcinogenesis ◽

Therapeutic Regime

Prostate cancer represents a major health issue and its incidence is rising globally. In developed countries, prostate cancer is the most frequently diagnosed cancer and the second most common cause of death from cancer in men. Androgen deprivation reduces tumour activity in approx. 80% of patients with advanced disease, but most tumours relapse within 2 years to an incurable hormone-resistant state. Even for patients with early disease at the time of diagnosis, a proportion of patients will unfortunately develop relapsed disease following radical therapy. Treatment options for patients with hormone-resistant prostate cancer are very limited and, even with toxic therapy, such as docetaxel, the life expectancy is only improved by a median of 2 months. Advances in molecular oncology have identified key signalling pathways that are considered to be driving events in prostate carcinogenesis. The activation of multiple signalling pathways increases further the possibility of cross-talk among ‘linear’ signalling cascades. Hence signalling networks that may incorporate distinct pathways in prostate cancer, particularly in hormone-resistant disease, are increasingly appreciated in drug development programmes. With the development of potent small-molecule inhibitors capable of specifically suppressing the activities of individual ‘linear’ cascades, it may be that, by combining these agents as guided by the molecular signature of prostate cancer, a more efficient therapeutic regime may be developed. Therefore the present review focuses on evidence of abnormal signalling in prostate cancer and the potential of these targets in drug development, and incorporates key findings of relevant clinical trials to date.

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