+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome

, : Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome. Cancer Research 76(17): 4948-4958

Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes. In this study, we computationally assembled a large virtual cohort (n = 1,321) of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1-3). We validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models. Analysis of subtype-specific gene expression patterns in independent datasets derived from luminal and basal cell models provides evidence that PCS1 and PCS2 tumors reflect luminal subtypes, while PCS3 represents a basal subtype. We show that PCS1 tumors progress more rapidly to metastatic disease in comparison with PCS2 or PCS3, including PSC1 tumors of low Gleason grade. To apply this finding clinically, we developed a 37-gene panel that accurately assigns individual tumors to one of the three PCS subtypes. This panel was also applied to circulating tumor cells (CTC) and provided evidence that PCS1 CTCs may reflect enzalutamide resistance. In summary, PCS subtyping may improve accuracy in predicting the likelihood of clinical progression and permit treatment stratification at early and late disease stages. Cancer Res; 76(17); 4948-58. ©2016 AACR.


PMID: 27302169

DOI: 10.1158/0008-5472.CAN-16-0902

Other references

Wehrspann, Jodie, 1999: Combine buying: can you justify?. Farm Industry News 32(9): 2

Flowers George C.; Isphording Wayne C., 1990: Environmental sedimentology of the Pontchartrain Estuary. Transactions - Gulf Coast Association of Geological Societies 40: 237-250

Oguzoglu,T.C., 2008: Border Disease. A review of the aetiology, transmission, pathogenesis, clinical and pathological findings, diagnosis and control of Border Disease, characterized by abortion and congenital abnormalities, in small ruminants is presented.

Nicolini, G.; Larcher, R.; Mattivi, F., 2004: Experiments concerning metal depletion in must and wine by Divergan HM. Divergan HM(TM), a vinylimidazole/vinylpyrrolidone co-polymer produced by BASF, was used in white juice and wine with several doses and different contact times. Metal depletion was more effective when Divergan HM(TM) was applied in juice than in w...

Yin Guan; Wang Xinglan; Liu Tianchou, 1997: Formed mechanism and water source composition on the runoff in the upper-middle course of the Lasa River, Xizang. Diqiu Xuebao = Acta Geoscientia Sinica 18, Suppl

Rizzo, N.; Hispard, E.; Dolbeault, S.; Dally, S.; Leverge, R.; Girre, C., 1997: Impact of long-term ethanol consumption on CYP1A2 activity. Ethanol is a well-known inducer of CYP2E1; whether or not it is an inducer of other cytochromes has not been investigated systematically. The aim of our study was to evaluate the impact of ethanol consumption on the activity of CYP1A2, which has b...

Ratnaraj, J.; Fernau, S.; Henrich, B.; Cheng, M.A.n, 2003: The Effects of Insertion of Orogastric Tube and Esophageal Stethoscope on Endotracheal Tube Cuff Pressures and Throat Discomfort. Introduction: Pressure exerted by the endotracheal tube cuff on the tracheal mucosa can cause ischemia if the pressure exceeds capillary pressure. Earlier works suggest that endotracheal cuff pressure (ETCP) be kept between 20-22mmHg to prevent tr...

Sridhar, M.K.; Adeoye, G.O.; AdeOluwa, O.O., 2003: Alternate nitrogen amendments for organic fertilizers. The use of compost or manure in agriculture as an organic source of nutrients is common in many tropical, developing countries like Nigeria. One of the drawbacks of such materials is their low nitrogen (N) content (=1% N). Farmers commonly use che...

Pereira, M.S.; Candeias, J.A., 1971: The association of viruses with clinical pertussis. This study describes the results of attempts to grow viruses from per-nasal swabs taken from 136 children with clinical pertussis.Altogether 37 strains of a variety of different viruses were isolated. Adenovirus was the most frequent, making up 30...

Dumas, F.; Kierzek, G.; Pourriat, J.-L., 2010: Infezioni cutanee. Batteriche, le ectoparassitosi e le micosi sono responsabili di patologie frequenti, ma meno gravi, riscontrate in medicina d urgenza.