A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy
Background: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a m...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624000125 |
| _version_ | 1797317484069519360 |
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| author | Casper W.F. van Eijck Sergio Sabroso-Lasa Gaby J. Strijk Dana A.M. Mustafa Amine Fellah Bas Groot Koerkamp Núria Malats Casper H.J. van Eijck |
| author_facet | Casper W.F. van Eijck Sergio Sabroso-Lasa Gaby J. Strijk Dana A.M. Mustafa Amine Fellah Bas Groot Koerkamp Núria Malats Casper H.J. van Eijck |
| author_sort | Casper W.F. van Eijck |
| collection | DOAJ |
| description | Background: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. Methods: Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed. Results: Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker. Conclusions: Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC. |
| first_indexed | 2024-03-08T03:36:39Z |
| format | Article |
| id | doaj.art-df1c5e3be68c445b96c584f8bff8fe46 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-03-08T03:36:39Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-df1c5e3be68c445b96c584f8bff8fe462024-02-10T04:44:10ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862024-03-0149100975A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapyCasper W.F. van Eijck0Sergio Sabroso-Lasa1Gaby J. Strijk2Dana A.M. Mustafa3Amine Fellah4Bas Groot Koerkamp5Núria Malats6Casper H.J. van Eijck7Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Corresponding authors at: Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40 3015 GD, Rotterdam, The Netherlands.Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Centro de Investigación Biomédica en Red-Cáncer (CIBERONC), Madrid, SpainErasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The NetherlandsDepartment of Clinical Bioinformatics, Erasmus University Medical Center, Rotterdam, The NetherlandsErasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The NetherlandsDepartment of Surgery, Erasmus University Medical Center, Rotterdam, The NetherlandsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Centro de Investigación Biomédica en Red-Cáncer (CIBERONC), Madrid, SpainErasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain; Corresponding authors at: Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40 3015 GD, Rotterdam, The Netherlands.Background: Pancreatic ductal adenocarcinoma (PDAC) is often treated with FOLFIRINOX, a chemotherapy associated with high toxicity rates and variable efficacy. Therefore, it is crucial to identify patients at risk of early progression during treatment. This study aims to explore the potential of a multi-omics biomarker for predicting early PDAC progression by employing an in-depth mathematical modeling approach. Methods: Blood samples were collected from 58 PDAC patients undergoing FOLFIRINOX before and after the first cycle. These samples underwent gene (GEP) and inflammatory protein expression profiling (IPEP). We explored the predictive potential of exclusively IPEP through Stepwise (Backward) Multivariate Logistic Regression modeling. Additionally, we integrated GEP and IPEP using Bayesian Kernel Regression modeling, aiming to enhance predictive performance. Ultimately, the FOLFIRINOX IPEP (FFX-IPEP) signature was developed. Results: Our findings revealed that proteins exhibited superior predictive accuracy than genes. Consequently, the FFX-IPEP signature consisted of six proteins: AMN, BANK1, IL1RL2, ITGB6, MYO9B, and PRSS8. The signature effectively identified patients transitioning from disease control to progression early during FOLFIRINOX, achieving remarkable predictive accuracy with an AUC of 0.89 in an independent test set. Importantly, the FFX-IPEP signature outperformed the conventional CA19-9 tumor marker. Conclusions: Our six-protein FFX-IPEP signature holds solid potential as a liquid biomarker for the early prediction of PDAC progression during toxic FOLFIRINOX chemotherapy. Further validation in an external cohort is crucial to confirm the utility of the FFX-IPEP signature. Future studies should expand to predict progression under different chemotherapies to enhance the guidance of personalized treatment selection in PDAC.http://www.sciencedirect.com/science/article/pii/S1476558624000125BiomarkersGene Expression ProfilingfolfirinoxPancreatic NeoplasmsPrecision MedicineProtein Array Analysis |
| spellingShingle | Casper W.F. van Eijck Sergio Sabroso-Lasa Gaby J. Strijk Dana A.M. Mustafa Amine Fellah Bas Groot Koerkamp Núria Malats Casper H.J. van Eijck A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy Neoplasia: An International Journal for Oncology Research Biomarkers Gene Expression Profiling folfirinox Pancreatic Neoplasms Precision Medicine Protein Array Analysis |
| title | A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy |
| title_full | A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy |
| title_fullStr | A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy |
| title_full_unstemmed | A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy |
| title_short | A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy |
| title_sort | liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during folfirinox chemotherapy |
| topic | Biomarkers Gene Expression Profiling folfirinox Pancreatic Neoplasms Precision Medicine Protein Array Analysis |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624000125 |
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