Metabolomic biomarkers of pancreatic cancer: a meta-analysis study

Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures. Here, we attempted to externally replicate proposed metabolite biomarkers of PC reported by several other groups in an independent group of PC subjects. Our study design included a T2DM cohort that was used as a non-cancer control and a separate cohort diagnosed with colorectal cancer (CRC), as a cancer disease control to eliminate possible generic biomarkers of cancer. We used targeted mass spectrometry for quantitation of literature-curated metabolite markers and identified a biomarker panel that discriminates between normal controls (NC) and PC patients with high accuracy. Further evaluation of our model with CRC, however, showed a drop in specificity for the PC biomarker panel. Taken together, our study underscores the need for a more robust study design for cancer biomarker studies so as to maximize the translational value and clinical implementation.This work was supported by ACS IRG-92-152-17 pilot award number AWD4470404 to KU and AKC. The authors would like to acknowledge the Metabolomics Shared Resource in Georgetown University (Washington DC, USA) partially supported by NIH/NCI/CCSG grant P30-CA05100

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies

Metabolomic and lipidomic profiling identifies the role of the RNA editing pathway in endometrial carcinogenesis

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.This work was supported by the Spanish Ministry of Health (RD12/0036/0035), the Spanish Ministry of Economy and Competitivy (PI14/02043), the AECC (Grupos Estables de Investigacion 2011 - AECC- GCB 110333 REVE), the Fundació La Marató TV3 (2/C/2013), the CIRIT Generalitat de Catalunya (2014 SGR 1330) and the European Commission, 7th Framework Program, IRSES (PROTBIOFLUID –269285) – Belgium. Te Spanish Ministry of Economy and Competitiveness (IJCI-2015-25000) granted Dr. Colás and and the AGAUR Generalitat de Catalunya (2015FI_B00703) granted Tatiana Altadill. Te authors would like to acknowledge the Proteomics and Metabolomics Shared Resource partially supported by Cancer Center Support Grant NIH/NCI grant P30-CA051008. Te Institut de Salud Carlos III (FIS (PI13/01701)) also supported this project. Tissue samples were obtained with the support of “Xarxa Catalana de Bancs de Tumors” and “Plataforma de Biobancos” ISCIII (PT13/0010/0014)

Radiation Metabolomics: Current Status and Future Directions

Human exposure to ionizing radiation disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms and peripheral lymphocyte counts are of limited value as organ and tissue specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic ionizing radiation. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure

Metabolomic biomarkers of pancreatic cancer: a meta-analysis study.

Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures. Here, we attempted to externally replicate proposed metabolite biomarkers of PC reported by several other groups in an independent group of PC subjects. Our study design included a T2DM cohort that was used as a non-cancer control and a separate cohort diagnosed with colorectal cancer (CRC), as a cancer disease control to eliminate possible generic biomarkers of cancer. We used targeted mass spectrometry for quantitation of literature-curated metabolite markers and identified a biomarker panel that discriminates between normal controls (NC) and PC patients with high accuracy. Further evaluation of our model with CRC, however, showed a drop in specificity for the PC biomarker panel. Taken together, our study underscores the need for a more robust study design for cancer biomarker studies so as to maximize the translational value and clinical implementation

Metabolomic and lipidomic profiling identifies the role of the RNA editing pathway in endometrial carcinogenesis

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies