Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma (Mouse NAMPT targeted therapy)
Ontology highlight
ABSTRACT: NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma. Mouse NAMPT targeted therapy is reported in the current study MTBLS7252. Cell NAMPTi treatment is reported in MTBLS7251. Mouse NAD targeted time-course is reported in MTBLS7253.
INSTRUMENT(S): Capillary electrophoresis MS - positive, Capillary electrophoresis MS - negative
PROVIDER: MTBLS7252 | MetaboLights | 2023-10-10
REPOSITORIES: MetaboLights
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| KEIO-2021-0080_Anion_01_d2.mzML | Mzml | |||
| KEIO-2021-0080_Anion_03_d2.mzML | Mzml | |||
| KEIO-2021-0080_Anion_23_d2.mzML | Mzml | |||
| KEIO-2021-0080_Anion_24_d2.mzML | Mzml | |||
| KEIO-2021-0080_Anion_26_d2.mzML | Mzml |
Items per page: 5 1 - 5 of 58 |
Publications
Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma.
Nomura Miyuki M Ohuchi Mai M Sakamoto Yoshimi Y Kudo Kei K Yaku Keisuke K Soga Tomoyoshi T Sugiura Yuki Y Morita Mami M Hayashi Kayoko K Miyahara Shuko S Sato Taku T Yamashita Yoji Y Ito Shigemi S Kikuchi Naohiko N Sato Ikuro I Saito Rintaro R Yaegashi Nobuo N Fukuhara Tatsuro T Yamada Hidekazu H Shima Hiroshi H Nakayama Keiichi I KI Hirao Atsushi A Kawasaki Kenta K Arai Yoichi Y Akamatsu Shusuke S Tanuma Sei-Ichi SI Sato Toshiro T Nakagawa Takashi T Tanuma Nobuhiro N
Nature communications 20231213 1
Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulat ...[more]
Similar Datasets
Project description:<p>NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent <em>de novo</em> NAD synthesis, promoting NAMPTi susceptibility <em>in vitro</em>. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.</p><p><br></p><p><strong>Cell NAMPTi treatment </strong>is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7251' rel='noopener noreferrer' target='_blank'><strong>MTBLS7251</strong></a>.</p><p><strong>Mouse NAMPT targeted therapy</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7252' rel='noopener noreferrer' target='_blank'><strong>MTBLS7252</strong></a>.</p><p><strong>Mouse NAD targeted time-course</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7253' rel='noopener noreferrer' target='_blank'><strong>MTBLS7253</strong></a>.</p>
2023-10-10 | MTBLS7251 | MetaboLights
Project description:<p>NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.</p><p><br></p><p><strong>Mouse NAD targeted time-course</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7253' rel='noopener noreferrer' target='_blank'><strong>MTBLS7253</strong></a>.</p><p><strong>Cell NAMPTi treatment</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7251' rel='noopener noreferrer' target='_blank'><strong>MTBLS7251</strong></a>.</p><p><strong>Mouse NAMPT targeted therapy</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7252' rel='noopener noreferrer' target='_blank'><strong>MTBLS7252</strong></a>.</p>
2023-10-10 | MTBLS7253 | MetaboLights
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1333, 58 lipid mediator standards were used to study the lipid fragmentation, build optimal collision energy models, create in-silico spectral libraries and spike-in as internal standards. They were purchased from Cayman Chemical (Ann Arbor, Michigan, USA). Lipid fragment masses of mediators were validated with the Metlin database (https://metlin.scripps.edu/).</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-07-16 | MSV000085765 | GNPS
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1334, 55 lipid mediator standards were used to study the lipid fragmentation on the Agilent QTof 6545 MS platform (Agilent Technologies, Waldbronn, Germany), build optimal collision energy models and create an in-silico spectral library for use with LipidCreator. Lipid fragment masses of mediators were validated with the Metlin database (https://metlin.scripps.edu/).</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/mtbls1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-07-14 | MSV000085747 | GNPS
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1382, to validate lipid mediator species identified with the Qtrap instrument (<a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>https://www.ebi.ac.uk/metabolights/MTBLS1381</a>), the Thermo QEx HF was used to perform high resolution MS full scan (HR-FS) and data independent acquisition (DIA) analyses between 200-400 m/z with a 20 m/z step size. DIA method preparation and data analysis were performed with Skyline. We used LipidCreator as an external tool in Skyline to generate a collision-energy specific transition list for the mediators 12-HETE, 13-HODE, 15-HETE, arachidonic acid (AA),<strong> </strong>docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and thromboxane B2 (TXB2) and their deuterated counterparts 12-HETE-d8, 13-HODE-d4, 15-HETE-d8, AA-d8, DHA-d5, EPA-d5 and TXB2-d4, at a normalized collision energy NCE=21. We also used LipidCreator's relative fragment intensity prediction model to generate a custom spectral library for the light and heavy mediators. We transfered both the transition list and the spectral library directly from LipidCreator to Skyline and exported the dot product values after manual fragment peaks review.</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-06-26 | MSV000085632 | GNPS
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1381, to validate the performance and accuracy of the transition lists provided by LipidCreator and their applicabability on other MS platforms, we used the transition lists for targeted profiling of lipid mediators in human platelet material. Platelets were stimulated with 0.01 U/ml thrombin, 1 U/ml thrombin, 1 µg/ml CRP or 5 µg/ml CRP for 5 min. The MS profiling of unstimulated and stimulated platelet material (pellet and supernatant) was performed after HPLC separation on an AB Sciex QTrap 6500 (Applied Biosystems, Darmstadt, Germany) in negative mode. Samples were measured in triplicates, interspersed with blank and standard runs.</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-07-14 | MSV000085743 | GNPS
Project description:<p>Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.</p><p><br></p><p>In MTBLS1376, to validate the performance and accuracy of the transition lists provided by LipidCreator, we validated our theoretical calculations and the transition lists computed by LipidCreator experimentally, monitoring true and false targets on the model organism Saccharomyces <em>cerevisiae</em>. The lipidome of the yeast S. <em>cerevisiae</em> is well described and has been thoroughly investigated before. It has a limited number of fatty acyls and double bonds, and certain fatty acyls and lipid classes do not occur in it, which is important for our consecutive false identification calculations. Therefore, the yeast matrix from the theoretical calculation, 21 target lipids and 21 decoy lipids from commercially available lipid standards that are known to not be present in the yeast lipidome were selected. Based on our previous results, none of the lipid species was redundant among all three sets.</p><p><br></p><p>Studies linked to this manuscript include;</p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1333' rel='noopener noreferrer' target='_blank'>MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HF</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1334' rel='noopener noreferrer' target='_blank'>MTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTof</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1369' rel='noopener noreferrer' target='_blank'>MTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1375' rel='noopener noreferrer' target='_blank'>MTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standard</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1376' rel='noopener noreferrer' target='_blank'>MTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identification</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1381' rel='noopener noreferrer' target='_blank'>MTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator Profiling</a></p><p><a href='https://www.ebi.ac.uk/metabolights/MTBLS1382' rel='noopener noreferrer' target='_blank'>MTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation</a></p>
2020-07-31 | MSV000085865 | GNPS
Project description:<p>Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients.</p><p><br></p><p><strong>UPLC-MS HILIC POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1122' rel='noopener noreferrer' target='_blank'><strong>MTBLS1122</strong></a>.</p><p><strong>UPLC-MS HILIC NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1124' rel='noopener noreferrer' target='_blank'><strong>MTBLS1124</strong></a>.</p><p><strong>UPLC-MS RP POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1129' rel='noopener noreferrer' target='_blank'><strong>MTBLS1129</strong></a>.</p><p><strong>UPLC-MS RP NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1130' rel='noopener noreferrer' target='_blank'><strong>MTBLS1130</strong></a>.</p>
2020-03-19 | MTBLS1129 | MetaboLights
Project description:<p>Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients.</p><p><br></p><p><strong>UPLC-MS HILIC POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1122' rel='noopener noreferrer' target='_blank'><strong>MTBLS1122</strong></a>.</p><p><strong>UPLC-MS HILIC NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1124' rel='noopener noreferrer' target='_blank'><strong>MTBLS1124</strong></a>.</p><p><strong>UPLC-MS RP POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1129' rel='noopener noreferrer' target='_blank'><strong>MTBLS1129</strong></a>.</p><p><strong>UPLC-MS RP NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1130' rel='noopener noreferrer' target='_blank'><strong>MTBLS1130</strong></a>.</p>
2020-03-19 | MTBLS1124 | MetaboLights
Project description:<p>Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients.</p><p><br></p><p><strong>UPLC-MS HILIC POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1122' rel='noopener noreferrer' target='_blank'><strong>MTBLS1122</strong></a>.</p><p><strong>UPLC-MS HILIC NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1124' rel='noopener noreferrer' target='_blank'><strong>MTBLS1124</strong></a>.</p><p><strong>UPLC-MS RP POS assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1129' rel='noopener noreferrer' target='_blank'><strong>MTBLS1129</strong></a>.</p><p><strong>UPLC-MS RP NEG assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1130' rel='noopener noreferrer' target='_blank'><strong>MTBLS1130</strong></a>.</p>
2020-03-19 | MTBLS1130 | MetaboLights