Appl Biochem Biotechnol DOI 10.1007/s12010-014-0955-6
Metabolomics Approaches and Applications in Prostate Cancer Research Aihua Zhang & Guangli Yan & Ying Han & Xijun Wang
Received: 7 April 2013 / Accepted: 9 May 2014 # Springer Science+Business Media New York 2014
Abstract Prostate cancer is a leading cause of cancer deaths in men worldwide. Although prostate-specific antigen (PSA) has been extensively used as a serum biomarker to detect prostate cancer, this screening method has suffered from a lack of specificities and sensitivities. The successful prevention and treatment of prostate cancer relies on the early and accurate detection of the disease; therefore, more sensitive biomarkers are urgently needed. Prostate has long been known to exhibit unique metabolite profiles, fortunately, metabolomics, the study of all metabolites produced in the body, can be considered most closely related to a patient’s phenotype. It may provide clinically useful biomarkers applied toward identifying metabolic alterations in prostate cancer and has introduced new insights into the pathology of prostate cancer. This advanced bioanalytic method may now open door for diagnostics. Metabolomics has a great and largely potential in the field of disease, and the analysis of the cancer metabolome to identify novel biomarkers and targets can now be undertaken in many research laboratories. In this review, we take a closer look at the metabolomics in the field of prostate cancer and highlight the interesting publications as references for the interested reader. Keywords Metabolomics . Prostate cancer . Biomarkers . Metabolites . Early diagnosis
Introduction Prostate cancer is the commonest solid organ malignancy diagnosed in men in the world [1]. Worldwide, the number of prostate cancer cases is approaching one million, and it is the sixth leading cause of cancer deaths in men. Both incidence and mortality are increasing in many countries [2]. Testing with serum prostate-specific antigen (PSA) has contributed to decreases in prostate cancer mortality in many developed countries, but the test and the diagnostic paradigm suffer from a number of problems such as low specificity of PSA and false-negative rate for prostate biopsy [3, 4]. Importantly, however, there are no markers currently available, to predict prostate cancer in early diagnosis. The diagnosis and management of prostate cancer A. Zhang (*) : G. Yan : Y. Han : X. Wang (*) Department of Pharmaceutical Analysis, Key Laboratory of Metabolomics and Chinmedomics, National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, Heping Road, Harbin 150010, China e-mail: [email protected] e-mail: [email protected]
Appl Biochem Biotechnol
continues to be an overwhelming challenge. Because small changes in living systems can lead to large changes in metabolite levels, the metabolome can be regarded as the amplified output of a biological system [5, 6]. Monitoring certain metabolite levels in body fluids has become an important way to detect early stages in prostate cancer [7]. Moreover, metabolomics, a dynamic portrait of the metabolic status of living systems, is likely to be used to screen for potential diagnostic and prognostic biomarkers of prostate cancer [8]. Metabolomics based the study of global changes in biomolecules in a disease in a highthroughput manner and hence are well poised to understand the complex changes which led to disease. By applying advanced analytical and statistical tools, metabolomics involves the comprehensive profiling of the full complement of low-molecular-weight compounds in a biological system and can be used to identify new predictive and prognostic markers and to discover new targets for future therapeutic interventions [9–11]. In the last decade, advances in metabolomics have been applied toward identifying metabolic alterations in prostate cancer that may provide clinically useful biomarkers [12]. Advances in technology and bioinformatics have led to the application of metabolomic profiling to prostate cancer—the high-throughput evaluation of a large complement of metabolites in the prostate and how they are altered by disease perturbations [13]. Recently, high profile publications have drawn attention to the potential of metabolomic analysis to identify biomarkers for early detection or disease progression from readily accessible body fluids as well as tissue specimens from biopsy and surgery [14, 15]. Metabolomics approach will begin to enter the mainstream of cancer diagnostics and therapeutics. In this review, we intend to explore the potential role of metabolomics in understanding prostate cancer process and highlight the potential value of metabolomics for the predictive biomarkers.
Metabolomics Technologies: The Metabolite Hunter Metabolome is a data-rich source of information concerning all the low-molecular-weight metabolites in a biofluid, which can indicate early biological changes to the host due to perturbations in metabolic pathways. The emerging field of metabolomics, in which a large number of small-molecule metabolites from body fluids or tissues are detected quantitatively in a single step, promises immense potential for early diagnosis, for therapy monitoring, and for understanding the pathogenesis of many diseases [16]. Technological developments are the driving force for advances in metabolomics and identifying novel changes in specific metabolites. A key task in cancer medicine is to detect the disease as early as possible. In order to achieve this, many new technologies have been developed for cancer biomarker discovery [17]. A combined analytical approach can improve the potential for providing reliable methods to detect metabolic profile alterations in a biological specimen. No single analytical method can accommodate the chemical diversity of the entire metabolome; therefore, a multiplatform method may provide a comprehensive understanding of metabolic alterations [18–20]. An improved metabolic profile obtained by combining MS and NMR approach could achieve more accurate disease detection and gain more insight regarding prostate cancer mechanisms [21].
Metabolic Characteristics of Prostate Cancer Many men who develop a prostate tumor never exhibit symptoms in the early stage of the disease or even before it spreads to other parts of the body, such as bones and lymph nodes.
Appl Biochem Biotechnol
Therefore, the successful prevention and treatment of prostate cancer relies on the early and accurate detection of the disease. Prostate-specific antigen has been extensively used as a serum biomarker to detect prostate tumors; however, this method has suffered from a lack of specificities and sensitivities [22]. Therefore, there is an underlying necessity to discover specific markers that may serve as molecular targets for the imaging of prostate cancer. Metabolomics provides a means for non-invasive screening of tumorassociated perturbations in metabolism [23–25]. It will clarify the metabolic pathways associated with progression of diseases and will also assist in identifying surrogate biomarkers for preventative or therapeutic approaches for prostate cancer [26]. Over the last few years, there has been a rapidly growing number of metabolomic applications aimed at finding biomarkers which could assist diagnosis, provide therapy guidance, and evaluate response to therapy for particular prostate cancer [27]. Understanding the metabolite pathways may insight into therapeutic mechanism and provides potential therapeutic targets [28–30].
Bringing Metabolomics into Prostate Cancer: The Sooner, The Better Prostate cancer is one of the most commonly diagnosed cancers and causes of cancer-related deaths worldwide. Studies have demonstrated that patient outcome is substantially influenced by cancer stage at the time of diagnosis [31]. For reasons largely unknown, the incidence of prostate cancer has increased in the last two decades, in spite or perhaps because of a concomitant increase in PSA screening that generally suffers from poor patient compliance. While PSA is acknowledged not to be an ideal biomarker for prostate cancer detection, it is however widely used by physicians due to lack of an alternative. Thus, the identification of biomarkers that can complement or replace PSA represents a major goal for prostate cancer research. It is important to develop effective methods for early diagnosis as well as for precise staging of this disease process. The 5-year survival rate for prostate cancer caught early is about 50 %—but catching it early is incredibly difficult, because symptoms typically appear only during advanced stages of disease. Once the cancer has spread, the survival rate drops to just 1 %. It is imperative to develop an ideal screening test which should be non-invasive with high sensitivity and specificity. Metabolomics promises to be a valuable tool in the early detection of prostate cancer that may enable earlier treatment and improved clinical outcomes [11, 32, 33]. Advantages of metabolomics over other “omics,” include its high sensitivity and its ability to enable the analysis of relatively few metabolites compared with the unwieldy number of corresponding genes or mRNA molecules [34]. Potential roles for metabolomics in the clinical trials of prostate cancer include biomarker discovery and validation, molecular target discovery, therapy decisions, and patient monitoring [35–37]. Recently, sarcosine, proline, kynurenine, uracil, and glycerol 3-phosphate were found in higher concentrations in metastatic prostate cancer urine samples. By measuring all five of these metabolites, doctors may be better able to diagnose prostate cancer with high accuracy. In a study, a novel method was developed to quantify the urinary metabolites in urine samples by using liquid chromatography-mass spectrometry (LC-MS). The technique developed is simple, fast, and sensitive and can be used for quantifying metabolites in urine samples for potential early cancer screening [38]. Scientists hope metabolomics will help detect cancer early, yield novel insights into prostate cancer processes, and that these insights will eventually translate into clinical applications that will pave the way from current medical routine to the ideal of personalized medicine [39].
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Metabolomics Applications in Prostate Cancer Early detection of prostate cancer is the only means to impact long-term survival, but screening methods are lacking. Given the complex nature of prostate cancer, metabolomics methods show promise to identify disease-specific molecular fingerprints [40]. Technological advances have made and will continue to make possible earlier, more accurate, less-invasive diagnoses, all while enhancing our understanding of the root causes of disease. Recently, several molecules were found to be specifically expressed in prostate cancer, and these novel molecular markers are reported to improve the sensitivity of cytology or biopsy. A recent study showed that sarcosine may be potentially useful for the diagnosis and prognosis of prostate cancer. The diagnostic value of sarcosine for prostate cancer was validated and evaluated by urine metabolomic profiles in patients with prostate cancer in comparison of non-cancerous control [41]. GC/MS (gas chromatography/mass spectrometry) was utilized to obtain the urinary metabolomic information in 20 prostate cancer patients. Diagnostic models for prostate cancer were constructed using principal component analysis and were assessed with receiver-operating characteristic curves. Results showed that the urinary sarcosine level has no statistical difference between the prostate cancer group and the control group. In addition, nine metabolomic markers between the prostate cancer group and the healthy male group were selected, which constructed a diagnostic model with a high area under the curve value of 0.9425 [41]. Urinary metabolomic panel based on GC/MS assay may potentially become a diagnostic tool for prostate cancer. In a study, Wu et al. evaluated five whole prostates removed during prostatectomy from biopsy-proven cancer patients [42]. Localized, multi-cross-sectional, multivoxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous intact tissue analyses. This calculated malignancy index is linearly correlated with lesion size and demonstrates a 93 to 97 % overall accuracy for detecting the presence of prostate cancer lesions, suggesting the potential clinical utility of this approach. Huang et al. used the LC-MS-based metabolomic technique to identify serum biomarkers indicative of disease progression and therapeutic benefit [43]. Seven metabolites, including deoxycholic acid, glycochenodeoxycholate, L-tryptophan, docosapentaenoic acid, arachidonic acid, deoxycytidine triphosphate, and pyridinoline, differed significantly between untreated prostate cancer patients and healthy controls. These metabolites maybe serve as predictive biomarkers for assessing the therapeutic response of prostate cancer patients. The potential of tissue metabolomic profiles was measured with ex vivo spectroscopy to identify prostate cancer aggressiveness in terms of cancer recurrence [44]. By applying the coefficients from principal component analysis in metabolomics, recurrence was predicted with an accuracy of 78 %. With further study, it may greatly contribute to the future design of clinical strategy for personalized treatment of prostate cancer patients. A number of other metabolic changes are found in prostate cancer. Using a combination of highthroughput liquid-and-gas-chromatography-based mass spectrometry, Sreekumar et al. profiled more than 1,126 metabolites in clinical samples related to prostate cancer [23]. The unbiased metabolomic profile was able to distinguish benign prostate, clinically localized prostate cancer, and metastatic disease. Sarcosine was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. It revealed sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity by profiling the metabolomic alterations of prostate cancer progression. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests.
Appl Biochem Biotechnol
Conclusions and Future Perspectives Elimination of cancer in the twenty-first century is likely to depend not only on more effective individualized treatment but also upon earlier detection and prevention of cancer. The burden of prostate cancer is growing worldwide, and with it, a more desperate need for better tools to detect, diagnose, and monitor the disease is required. Considering the low sensitivity of PSA testing, it is widely agreed that reliable markers of the prostate cancer are required to facilitate diagnosis and timely treatment. Metabolomics, the non-targeted interrogation of small molecules in a biological sample, is an ideal technology for identifying diagnostic biomarkers, owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. In summary, the quantitative nature of data obtained from metabolomics-based studies allows for development of diagnostic and prognostic biomarkers based on changes in metabolite expression to facilitate the detection of prostate tumor signatures. We hope that it will eventually lead to diagnostic toolkits that will facilitate a much more precise predictive and prognostic assessment for prostate cancer. Acknowledgments This work was supported by the grants from the Key Program of Natural Science Foundation of State (Grant No. 90709019, 81173500, 81373930, 81302905, 81102556, 81202639), National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant No. 2011BAI03B03, 2011BAI03B06, 2011BAI03B08), National Key Subject of Drug Innovation (Grant No. 2009ZX09502-005), and Foundation of Heilongjiang University of Chinese Medicine (Grant no. 201209). Conflict of Interests The authors have declared that they have no competing interests.
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Metabolomics Approaches and Applications in Prostate Cancer Research Aihua Zhang & Guangli Yan & Ying Han & Xijun Wang
Received: 7 April 2013 / Accepted: 9 May 2014 # Springer Science+Business Media New York 2014
Abstract Prostate cancer is a leading cause of cancer deaths in men worldwide. Although prostate-specific antigen (PSA) has been extensively used as a serum biomarker to detect prostate cancer, this screening method has suffered from a lack of specificities and sensitivities. The successful prevention and treatment of prostate cancer relies on the early and accurate detection of the disease; therefore, more sensitive biomarkers are urgently needed. Prostate has long been known to exhibit unique metabolite profiles, fortunately, metabolomics, the study of all metabolites produced in the body, can be considered most closely related to a patient’s phenotype. It may provide clinically useful biomarkers applied toward identifying metabolic alterations in prostate cancer and has introduced new insights into the pathology of prostate cancer. This advanced bioanalytic method may now open door for diagnostics. Metabolomics has a great and largely potential in the field of disease, and the analysis of the cancer metabolome to identify novel biomarkers and targets can now be undertaken in many research laboratories. In this review, we take a closer look at the metabolomics in the field of prostate cancer and highlight the interesting publications as references for the interested reader. Keywords Metabolomics . Prostate cancer . Biomarkers . Metabolites . Early diagnosis
Introduction Prostate cancer is the commonest solid organ malignancy diagnosed in men in the world [1]. Worldwide, the number of prostate cancer cases is approaching one million, and it is the sixth leading cause of cancer deaths in men. Both incidence and mortality are increasing in many countries [2]. Testing with serum prostate-specific antigen (PSA) has contributed to decreases in prostate cancer mortality in many developed countries, but the test and the diagnostic paradigm suffer from a number of problems such as low specificity of PSA and false-negative rate for prostate biopsy [3, 4]. Importantly, however, there are no markers currently available, to predict prostate cancer in early diagnosis. The diagnosis and management of prostate cancer A. Zhang (*) : G. Yan : Y. Han : X. Wang (*) Department of Pharmaceutical Analysis, Key Laboratory of Metabolomics and Chinmedomics, National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, Heping Road, Harbin 150010, China e-mail: [email protected] e-mail: [email protected]
Appl Biochem Biotechnol
continues to be an overwhelming challenge. Because small changes in living systems can lead to large changes in metabolite levels, the metabolome can be regarded as the amplified output of a biological system [5, 6]. Monitoring certain metabolite levels in body fluids has become an important way to detect early stages in prostate cancer [7]. Moreover, metabolomics, a dynamic portrait of the metabolic status of living systems, is likely to be used to screen for potential diagnostic and prognostic biomarkers of prostate cancer [8]. Metabolomics based the study of global changes in biomolecules in a disease in a highthroughput manner and hence are well poised to understand the complex changes which led to disease. By applying advanced analytical and statistical tools, metabolomics involves the comprehensive profiling of the full complement of low-molecular-weight compounds in a biological system and can be used to identify new predictive and prognostic markers and to discover new targets for future therapeutic interventions [9–11]. In the last decade, advances in metabolomics have been applied toward identifying metabolic alterations in prostate cancer that may provide clinically useful biomarkers [12]. Advances in technology and bioinformatics have led to the application of metabolomic profiling to prostate cancer—the high-throughput evaluation of a large complement of metabolites in the prostate and how they are altered by disease perturbations [13]. Recently, high profile publications have drawn attention to the potential of metabolomic analysis to identify biomarkers for early detection or disease progression from readily accessible body fluids as well as tissue specimens from biopsy and surgery [14, 15]. Metabolomics approach will begin to enter the mainstream of cancer diagnostics and therapeutics. In this review, we intend to explore the potential role of metabolomics in understanding prostate cancer process and highlight the potential value of metabolomics for the predictive biomarkers.
Metabolomics Technologies: The Metabolite Hunter Metabolome is a data-rich source of information concerning all the low-molecular-weight metabolites in a biofluid, which can indicate early biological changes to the host due to perturbations in metabolic pathways. The emerging field of metabolomics, in which a large number of small-molecule metabolites from body fluids or tissues are detected quantitatively in a single step, promises immense potential for early diagnosis, for therapy monitoring, and for understanding the pathogenesis of many diseases [16]. Technological developments are the driving force for advances in metabolomics and identifying novel changes in specific metabolites. A key task in cancer medicine is to detect the disease as early as possible. In order to achieve this, many new technologies have been developed for cancer biomarker discovery [17]. A combined analytical approach can improve the potential for providing reliable methods to detect metabolic profile alterations in a biological specimen. No single analytical method can accommodate the chemical diversity of the entire metabolome; therefore, a multiplatform method may provide a comprehensive understanding of metabolic alterations [18–20]. An improved metabolic profile obtained by combining MS and NMR approach could achieve more accurate disease detection and gain more insight regarding prostate cancer mechanisms [21].
Metabolic Characteristics of Prostate Cancer Many men who develop a prostate tumor never exhibit symptoms in the early stage of the disease or even before it spreads to other parts of the body, such as bones and lymph nodes.
Appl Biochem Biotechnol
Therefore, the successful prevention and treatment of prostate cancer relies on the early and accurate detection of the disease. Prostate-specific antigen has been extensively used as a serum biomarker to detect prostate tumors; however, this method has suffered from a lack of specificities and sensitivities [22]. Therefore, there is an underlying necessity to discover specific markers that may serve as molecular targets for the imaging of prostate cancer. Metabolomics provides a means for non-invasive screening of tumorassociated perturbations in metabolism [23–25]. It will clarify the metabolic pathways associated with progression of diseases and will also assist in identifying surrogate biomarkers for preventative or therapeutic approaches for prostate cancer [26]. Over the last few years, there has been a rapidly growing number of metabolomic applications aimed at finding biomarkers which could assist diagnosis, provide therapy guidance, and evaluate response to therapy for particular prostate cancer [27]. Understanding the metabolite pathways may insight into therapeutic mechanism and provides potential therapeutic targets [28–30].
Bringing Metabolomics into Prostate Cancer: The Sooner, The Better Prostate cancer is one of the most commonly diagnosed cancers and causes of cancer-related deaths worldwide. Studies have demonstrated that patient outcome is substantially influenced by cancer stage at the time of diagnosis [31]. For reasons largely unknown, the incidence of prostate cancer has increased in the last two decades, in spite or perhaps because of a concomitant increase in PSA screening that generally suffers from poor patient compliance. While PSA is acknowledged not to be an ideal biomarker for prostate cancer detection, it is however widely used by physicians due to lack of an alternative. Thus, the identification of biomarkers that can complement or replace PSA represents a major goal for prostate cancer research. It is important to develop effective methods for early diagnosis as well as for precise staging of this disease process. The 5-year survival rate for prostate cancer caught early is about 50 %—but catching it early is incredibly difficult, because symptoms typically appear only during advanced stages of disease. Once the cancer has spread, the survival rate drops to just 1 %. It is imperative to develop an ideal screening test which should be non-invasive with high sensitivity and specificity. Metabolomics promises to be a valuable tool in the early detection of prostate cancer that may enable earlier treatment and improved clinical outcomes [11, 32, 33]. Advantages of metabolomics over other “omics,” include its high sensitivity and its ability to enable the analysis of relatively few metabolites compared with the unwieldy number of corresponding genes or mRNA molecules [34]. Potential roles for metabolomics in the clinical trials of prostate cancer include biomarker discovery and validation, molecular target discovery, therapy decisions, and patient monitoring [35–37]. Recently, sarcosine, proline, kynurenine, uracil, and glycerol 3-phosphate were found in higher concentrations in metastatic prostate cancer urine samples. By measuring all five of these metabolites, doctors may be better able to diagnose prostate cancer with high accuracy. In a study, a novel method was developed to quantify the urinary metabolites in urine samples by using liquid chromatography-mass spectrometry (LC-MS). The technique developed is simple, fast, and sensitive and can be used for quantifying metabolites in urine samples for potential early cancer screening [38]. Scientists hope metabolomics will help detect cancer early, yield novel insights into prostate cancer processes, and that these insights will eventually translate into clinical applications that will pave the way from current medical routine to the ideal of personalized medicine [39].
Appl Biochem Biotechnol
Metabolomics Applications in Prostate Cancer Early detection of prostate cancer is the only means to impact long-term survival, but screening methods are lacking. Given the complex nature of prostate cancer, metabolomics methods show promise to identify disease-specific molecular fingerprints [40]. Technological advances have made and will continue to make possible earlier, more accurate, less-invasive diagnoses, all while enhancing our understanding of the root causes of disease. Recently, several molecules were found to be specifically expressed in prostate cancer, and these novel molecular markers are reported to improve the sensitivity of cytology or biopsy. A recent study showed that sarcosine may be potentially useful for the diagnosis and prognosis of prostate cancer. The diagnostic value of sarcosine for prostate cancer was validated and evaluated by urine metabolomic profiles in patients with prostate cancer in comparison of non-cancerous control [41]. GC/MS (gas chromatography/mass spectrometry) was utilized to obtain the urinary metabolomic information in 20 prostate cancer patients. Diagnostic models for prostate cancer were constructed using principal component analysis and were assessed with receiver-operating characteristic curves. Results showed that the urinary sarcosine level has no statistical difference between the prostate cancer group and the control group. In addition, nine metabolomic markers between the prostate cancer group and the healthy male group were selected, which constructed a diagnostic model with a high area under the curve value of 0.9425 [41]. Urinary metabolomic panel based on GC/MS assay may potentially become a diagnostic tool for prostate cancer. In a study, Wu et al. evaluated five whole prostates removed during prostatectomy from biopsy-proven cancer patients [42]. Localized, multi-cross-sectional, multivoxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous intact tissue analyses. This calculated malignancy index is linearly correlated with lesion size and demonstrates a 93 to 97 % overall accuracy for detecting the presence of prostate cancer lesions, suggesting the potential clinical utility of this approach. Huang et al. used the LC-MS-based metabolomic technique to identify serum biomarkers indicative of disease progression and therapeutic benefit [43]. Seven metabolites, including deoxycholic acid, glycochenodeoxycholate, L-tryptophan, docosapentaenoic acid, arachidonic acid, deoxycytidine triphosphate, and pyridinoline, differed significantly between untreated prostate cancer patients and healthy controls. These metabolites maybe serve as predictive biomarkers for assessing the therapeutic response of prostate cancer patients. The potential of tissue metabolomic profiles was measured with ex vivo spectroscopy to identify prostate cancer aggressiveness in terms of cancer recurrence [44]. By applying the coefficients from principal component analysis in metabolomics, recurrence was predicted with an accuracy of 78 %. With further study, it may greatly contribute to the future design of clinical strategy for personalized treatment of prostate cancer patients. A number of other metabolic changes are found in prostate cancer. Using a combination of highthroughput liquid-and-gas-chromatography-based mass spectrometry, Sreekumar et al. profiled more than 1,126 metabolites in clinical samples related to prostate cancer [23]. The unbiased metabolomic profile was able to distinguish benign prostate, clinically localized prostate cancer, and metastatic disease. Sarcosine was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. It revealed sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity by profiling the metabolomic alterations of prostate cancer progression. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests.
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Conclusions and Future Perspectives Elimination of cancer in the twenty-first century is likely to depend not only on more effective individualized treatment but also upon earlier detection and prevention of cancer. The burden of prostate cancer is growing worldwide, and with it, a more desperate need for better tools to detect, diagnose, and monitor the disease is required. Considering the low sensitivity of PSA testing, it is widely agreed that reliable markers of the prostate cancer are required to facilitate diagnosis and timely treatment. Metabolomics, the non-targeted interrogation of small molecules in a biological sample, is an ideal technology for identifying diagnostic biomarkers, owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. In summary, the quantitative nature of data obtained from metabolomics-based studies allows for development of diagnostic and prognostic biomarkers based on changes in metabolite expression to facilitate the detection of prostate tumor signatures. We hope that it will eventually lead to diagnostic toolkits that will facilitate a much more precise predictive and prognostic assessment for prostate cancer. Acknowledgments This work was supported by the grants from the Key Program of Natural Science Foundation of State (Grant No. 90709019, 81173500, 81373930, 81302905, 81102556, 81202639), National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant No. 2011BAI03B03, 2011BAI03B06, 2011BAI03B08), National Key Subject of Drug Innovation (Grant No. 2009ZX09502-005), and Foundation of Heilongjiang University of Chinese Medicine (Grant no. 201209). Conflict of Interests The authors have declared that they have no competing interests.
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