Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer
Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC pat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/11/3020 |
| _version_ | 1797597819424473088 |
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| author | Hayato Muranaka Andrew Hendifar Arsen Osipov Natalie Moshayedi Veronica Placencio-Hickok Nicholas Tatonetti Aleksandr Stotland Sarah Parker Jennifer Van Eyk Stephen J. Pandol Neil A. Bhowmick Jun Gong |
| author_facet | Hayato Muranaka Andrew Hendifar Arsen Osipov Natalie Moshayedi Veronica Placencio-Hickok Nicholas Tatonetti Aleksandr Stotland Sarah Parker Jennifer Van Eyk Stephen J. Pandol Neil A. Bhowmick Jun Gong |
| author_sort | Hayato Muranaka |
| collection | DOAJ |
| description | Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, we analyzed plasma metabolites using high-performance liquid chromatography–mass spectrometry from 31 cachectic, advanced-PC subjects enrolled into the PANCAX-1 (NCT02400398) prospective trial to receive a jejunal tube peptide-based diet for 12 weeks and who were planned for palliative chemotherapy. Overall, there were statistically significant differences in the levels of intermediates of multiple metabolic pathways in pts with a partial response (PR)/stable disease (SD) vs. progressive disease (PD) to chemotherapy. When stratified by the chemotherapy regimen, PD after 5-fluorouracil-based chemotherapy (e.g., FOLFIRINOX) was associated with decreased levels of amino acids (AAs). For gemcitabine-based chemotherapy (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis, the TCA cycle, nucleoside synthesis, and bile acid metabolism. These results demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced-PC patients for assessing the effect of enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of a patient’s response and warrant further study. |
| first_indexed | 2024-03-11T03:10:51Z |
| format | Article |
| id | doaj.art-bb44bdcda21948919eab4a1f2217b4c6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:51Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bb44bdcda21948919eab4a1f2217b4c62023-11-18T07:39:39ZengMDPI AGCancers2072-66942023-06-011511302010.3390/cancers15113020Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic CancerHayato Muranaka0Andrew Hendifar1Arsen Osipov2Natalie Moshayedi3Veronica Placencio-Hickok4Nicholas Tatonetti5Aleksandr Stotland6Sarah Parker7Jennifer Van Eyk8Stephen J. Pandol9Neil A. Bhowmick10Jun Gong11Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAAdvanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAPancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, we analyzed plasma metabolites using high-performance liquid chromatography–mass spectrometry from 31 cachectic, advanced-PC subjects enrolled into the PANCAX-1 (NCT02400398) prospective trial to receive a jejunal tube peptide-based diet for 12 weeks and who were planned for palliative chemotherapy. Overall, there were statistically significant differences in the levels of intermediates of multiple metabolic pathways in pts with a partial response (PR)/stable disease (SD) vs. progressive disease (PD) to chemotherapy. When stratified by the chemotherapy regimen, PD after 5-fluorouracil-based chemotherapy (e.g., FOLFIRINOX) was associated with decreased levels of amino acids (AAs). For gemcitabine-based chemotherapy (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis, the TCA cycle, nucleoside synthesis, and bile acid metabolism. These results demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced-PC patients for assessing the effect of enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of a patient’s response and warrant further study.https://www.mdpi.com/2072-6694/15/11/3020pancreatic cancerchemotherapyFOLFIRINOXgemcitabine/nab-paclitaxelplasma metabolomics |
| spellingShingle | Hayato Muranaka Andrew Hendifar Arsen Osipov Natalie Moshayedi Veronica Placencio-Hickok Nicholas Tatonetti Aleksandr Stotland Sarah Parker Jennifer Van Eyk Stephen J. Pandol Neil A. Bhowmick Jun Gong Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer Cancers pancreatic cancer chemotherapy FOLFIRINOX gemcitabine/nab-paclitaxel plasma metabolomics |
| title | Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer |
| title_full | Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer |
| title_fullStr | Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer |
| title_full_unstemmed | Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer |
| title_short | Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer |
| title_sort | plasma metabolomics predicts chemotherapy response in advanced pancreatic cancer |
| topic | pancreatic cancer chemotherapy FOLFIRINOX gemcitabine/nab-paclitaxel plasma metabolomics |
| url | https://www.mdpi.com/2072-6694/15/11/3020 |
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