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The potential impact of adding genetic markers to clinical parameters in managing high-risk prostate cancer patients.

ABSTRACT: PURPOSE:High-risk prostate cancer is a potentially lethal disease that is increasing in the diagnosis of prostate cancer patients. Compared to other prostate cancer patients (medium or low risk), management, diagnosis and treatment are not as successful among high-risk patients. Because the genetic characterization of prostate cancer patients is increasing, we aimed to determine whether genetic information in one of the primary associated genes, such as RNASEL (2', 5'-oligoadenylate-dependent RNase L), could be used as a biomarker to improve the quality of life and treatment among high-risk patients. The main objective is to identify genetic variants of RNASEL that could be associated with high-risk prostate cancer to improve the clinical managing of these patients. METHODS:A total of 231 prostate cancer patients were genotyped for 7 variants of RNASEL gene. Clinical information was obtained from medical examinations and genetic analysis (amplification and sequencing 7 variants of RNASEL gene) were performed by the researchers. Data were processed by statistical analysis (Chi square and logistic regression) using SPSS v.15.0. RESULTS:Comparisons between genotypes and clinical characteristics of patients revealed that individuals with GG in D541E, AA in R462Q and AG in I97L in RNASEL gene were high-risk patients according to the European Urology Guidelines. CONCLUSIONS:Genotyping the RNASEL gene with routine diagnostic techniques could confer a more precise diagnosis of high-risk prostate cancer patients and increase the diagnostic accuracy above the current rate of 70% due to the relation between the genetic variants of RNASEL gene and the risk of this cancer.

SUBMITTER: Alvarez-Cubero MJ

PROVIDER: S-EPMC3773101 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The potential impact of adding genetic markers to clinical parameters in managing high-risk prostate cancer patients.

Alvarez-Cubero Maria Jesus MJ Martinez-Gonzalez Luis Javier LJ Vazquez-Alonso Fernando F Saiz Maria M Alvarez Juan Carlos JC Lorente Jose Antonio JA Cozar Jose Manuel JM

SpringerPlus 20130908

<h4>Purpose</h4>High-risk prostate cancer is a potentially lethal disease that is increasing in the diagnosis of prostate cancer patients. Compared to other prostate cancer patients (medium or low risk), management, diagnosis and treatment are not as successful among high-risk patients. Because the genetic characterization of prostate cancer patients is increasing, we aimed to determine whether genetic information in one of the primary associated genes, such as RNASEL (2', 5'-oligoadenylate-depe ...[more]

PMID: 24046815

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Project description:Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear. We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels. Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer.

Project description:The use of diets with increased fibre content from alternative feedstuffs less digestible for pigs is a solution considered to limit the impact of increased feed costs on pig production. This study aimed at determining the impact of an alternative diet on genetic parameters for growth, feed efficiency, carcass composition and meat quality traits. A total of 783 Large White pigs were fed a high-fibre (HF) diet and 880 of their sibs were fed a conventional (CO) cereal-based diet. Individual daily feed intake, average daily gain, feed conversion ratio and residual feed intake were recorded as well as lean meat percentage (LMP), carcass yield (CY) and meat quality traits. Pigs fed the CO diet had better performances for growth and feed efficiency than pigs fed the HF diet. They also had lower LMP and higher CY. In addition, pigs fed the CO diet had lower loin percentage and ham percentage and higher backfat percentage. No differences were observed in meat quality traits between diets, except for a* and b* values. For all traits, the genetic variances and heritability were not different between diets. Genetic correlations for traits between diets ranged between 0.80 ± 0.13 and 0.99 ± not estimable, and none were significantly different from 0.99, except for LMP. Thus, traits in both diets were considered as mainly affected by similar sets of genes in the two diets. A genetic correlation lower than 0.80 would justify redesigning the breeding scheme; however, some genetic correlations did not differ significantly from 0.80 either. Therefore, larger populations are needed for a more definitive answer regarding the design of the breeding scheme. To further evaluate selection strategies, a production index was computed within diets for the 29 sires with estimated breeding value reliability higher than 0.35. The rank correlation between indices estimated in the CO and in the HF diet was 0.72. Altogether, we concluded that limited interaction between feed and genetics could be evidenced, and based on these results there is no need to change pig selection schemes to adapt to the future increased use of alternative feedstuffs in production farms.

Dataset Information

The potential impact of adding genetic markers to clinical parameters in managing high-risk prostate cancer patients.

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The potential impact of adding genetic markers to clinical parameters in managing high-risk prostate cancer patients.

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