Gene expression correlates of clinical prostate cancer behavior

Abstract

Prostate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion were found, a set of genes was identified that strongly correlated with the state of tumor differentiation as measured by Gleason score. Moreover, a model using gene expression data alone accurately predicted patient outcome following prostatectomy. These results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis.

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

“…Although multiple prior studies have related genomic markers to PCa clinical outcomes [17][18][19][20]51], the development of GPS specifically addresses the impact of tumor sampling in predicting aggressive PCa and included central pathology review and a large number of clinical recurrence events providing robust statistical power. By adding independent molecular information to established risk parameters, the GPS improves risk stratification at time of diagnosis and may favorably shift the balance of risks and benefits for men who are candidates for AS and facing challenging decisions regarding optimal management of localized PCa.…”

“…Although many groups have demonstrated the potential of gene expression analysis to predict outcome in localized PCa [17][18][19][20], frequent genetic differences between regions of individual tumors and limited tumor sampling by needle biopsy pose challenges to molecular-based assays in PCa [21,22]. With these challenges in mind, we conducted two studies to identify genes for which expression in both prostatectomy and biopsy tissues consistently correlates with tumor aggressiveness regardless of multifocality, heterogeneity, or technical challenges associated with limited tumor obtained through biopsy.…”

Beyond tumorigenesis: cancer stem cells in metastasis

“…Applying genomic approaches, molecular signatures have been defined to successfully predict poor prognosis for patients due to the metastatic potential of solid tumors. This suggests that the metastasis gene program is shared by the majority of cancer cells found in primary tumors [113][114][115][116]. Presently, the functional relevance of those signature genes to the underlying mechanisms for cancer progression and metastasis is not immediately obvious, partially due to the lack of significant overlap among reported signatures.…”

In vivo regulation of p21 by the Kruppel-like factor 6 tumor-suppressor gene in mouse liver and human hepatocellular carcinoma

“…KLF6 dysregulation has been demonstrated in a number of human cancers including prostate (Narla et al, 2001;Chen et al, 2003), colorectal , non-smallcell lung (Ito et al, 2004), gastric (Cho et al, 2005), nasopharyngeal (Chen et al, 2002), hepatocellular (Kremer-Tal et al, 2004) and ovarian carcinomas (DiFeo et al, 2006b) as well as glioma (Jeng et al, 2003). Furthermore, decreased KLF6 mRNA expression is associated with reduced patient survival in prostate (Singh et al, 2002;Glinsky et al, 2004) and lung cancers (Kettunen et al, 2004). Interestingly, reconstitution of KLF6 decreases cell proliferation and reverts tumorigenicity in glioblastoma cell lines (Kimmelman et al, 2004).…”