Abstract

BackgroundProstate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related deaths in industrialized countries. Worldwide, an increase in prostate cancer incidence is expected due to an increased life-expectancy, aging of the population and improved diagnosis. Although the specific underlying mechanisms of prostate carcinogenesis remain unknown, prostate cancer is thought to result from a combination of genetic and environmental factors altering key cellular processes. To elucidate these complex interactions and to contribute to the understanding of prostate cancer progression and metastasis, analysis of large scale gene expression studies using bioinformatics approaches is used to decipher regulation of core processes.Methodology/Principal FindingsIn this study, a standardized quality control procedure and statistical analysis (http://www.arrayanalysis.org/) were applied to multiple prostate cancer datasets retrieved from the ArrayExpress data repository and pathway analysis using PathVisio (http://www.pathvisio.org/) was performed. The results led to the identification of three core biological processes that are strongly affected during prostate carcinogenesis: cholesterol biosynthesis, the process of epithelial-to-mesenchymal transition and an increased metabolic activity.ConclusionsThis study illustrates how a standardized bioinformatics evaluation of existing microarray data and subsequent pathway analysis can quickly and cost-effectively provide essential information about important molecular pathways and cellular processes involved in prostate cancer development and disease progression. The presented results may assist in biomarker profiling and the development of novel treatment approaches.

Highlights

  • Prostate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related morbidity and mortality in industrialized countries [1,2,3]

  • The specific underlying mechanisms of prostate carcinogenesis have not been unraveled yet, it is supposed that prostate cancer results from a combination of genetic and environmental factors, including several susceptibility genes for inherited prostate cancer, ethnicity and family history, as well as different dietary and life style factors [1,3,5,6,7]

  • Due to the complex etiology of prostate cancer, treatment options for prostate cancer patients depend on multiple factors, including a patient’s age and general health status, the prostate specific antigen (PSA) level, as well as the tumor grade and status

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Summary

Introduction

Prostate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related morbidity and mortality in industrialized countries [1,2,3]. It is estimated that 25–40% of men undergoing radical prostatectomy will have disease relapse, as detected by increasing serum levels of PSA [8] Another treatment option for prostate cancer is androgen ablation therapy that has become the standard treatment in advanced cases of prostate cancer. Androgen depletion is often associated with disease recurrence, as indicated by elevated PSA levels This recurrent form of prostate cancer is known as androgen-independent, an essentially untreatable form of prostate cancer that progresses and metastasizes. The specific underlying mechanisms of prostate carcinogenesis remain unknown, prostate cancer is thought to result from a combination of genetic and environmental factors altering key cellular processes To elucidate these complex interactions and to contribute to the understanding of prostate cancer progression and metastasis, analysis of large scale gene expression studies using bioinformatics approaches is used to decipher regulation of core processes

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