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In silico functional profiling of individual prostate cancer tumors: many genes, few functions.

ABSTRACT: Identification of genes that are differently expressed is a common approach used to analyze genetic mechanisms underlying cancer development. However, recent study results suggest that many such genes relate to a small number of biological functions. We hypothesized that analysis of these functions provides a better understanding of tumor biology than does actual identification of these genes.We re-analyzed publicly available gene expression data for paired samples of prostate tumor and adjacent normal tissue from the same patients to identify genes differently expressed in individual tumors and then used them to identify the functions.We found significant interindividual variation in the type and the number of functions. After adjusting for redundancy and nonspecificity of the functional terms, we identified seven functions. Several of them showed a strong association with clinical traits, e.g. age at diagnosis, preoperative prostate-specific antigen concentration, Gleason grade, and biochemical recurrence. Actin cytoskeleton was the function most frequently associated with clinical traits. Of note, the association between function and clinical traits was much stronger than that between the genes differently expressed and those traits.Different prostate tumors differ in their functional profiles. Functions of differently expressed genes are strongly associated with clinical traits. This suggests that analysis of functions of differently expressed genes may provide a better description of tumor biology than does analysis of the respective genes.

SUBMITTER: Gorlov IP

PROVIDER: S-EPMC3922615 | biostudies-literature | 2012 May-Jun

REPOSITORIES: biostudies-literature

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In silico functional profiling of individual prostate cancer tumors: many genes, few functions.

Gorlov Ivan P IP Byun Jinyoung J Logothetis Christopher J CJ

Cancer genomics & proteomics 20120501 3

<h4>Background</h4>Identification of genes that are differently expressed is a common approach used to analyze genetic mechanisms underlying cancer development. However, recent study results suggest that many such genes relate to a small number of biological functions. We hypothesized that analysis of these functions provides a better understanding of tumor biology than does actual identification of these genes.<h4>Materials and methods</h4>We re-analyzed publicly available gene expression data ...[more]

PMID: 22593245

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Project description:Most reintroduction and restocking programs consist of releasing captive-raised juveniles. The usefulness of these programs has been questioned, and therefore, quality control is advisable. However, evaluating restocking effectiveness is challenging because mortality estimation is required. Most methods for estimating mortality are based on tag recovery. In the case of fish, juveniles are tagged before release, and fishermen typically recover tags when fish are captured. The statistical models currently available for analyzing these data assume either constant mortality rates, fixed tag non-reporting rates, or both. Here, instead, we proposed a method that considers the mortality rate variability as a function of age/size of the released juveniles. Furthermore, the proposed method can disentangle natural from fishing mortality, analyzing the temporal distribution of the captures reported by fishermen from multiple release events. This method is demonstrated with a restocking program of a top-predator marine fish, the meagre (Argyrosomus regius), in the Balearic Islands. The estimated natural mortality just after release was very high for young fish (m0 = 0.126 day-1 for fish 180 days old), but it was close to zero for large/old fish. These large/old fish were more resilient to wild conditions, although a long time was needed to achieve a relevant reduction in natural mortality. Conversely, these large/old fish were more vulnerable to fishing, creating a trade-off in survival. The release age that maximizes the number of survivors after, for example, one year at liberty was estimated to be 1,173 days. However, the production cost of relatively old fish is high, and only a few fish can be produced and released within a realistic budget. Therefore, in the case of the meagre, increasing the number of released fish will have no or scarce effects on restocking success. Conversely, it is advisable implement measures to reduce the high natural mortality of young juveniles and/or the length of time needed to improve fish resilience.

Dataset Information

In silico functional profiling of individual prostate cancer tumors: many genes, few functions.

Publications

In silico functional profiling of individual prostate cancer tumors: many genes, few functions.

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