Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer
Background/AimsIt was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observation...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1488749/full |
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| author | Peder R. Braadland Peder R. Braadland Ingvild Farnes Ingvild Farnes Elin H. Kure Elin H. Kure Sheraz Yaqub Sheraz Yaqub Adrian McCann Per M. Ueland Per M. Ueland Knut Jørgen Labori Knut Jørgen Labori Johannes R. Hov Johannes R. Hov Johannes R. Hov |
| author_facet | Peder R. Braadland Peder R. Braadland Ingvild Farnes Ingvild Farnes Elin H. Kure Elin H. Kure Sheraz Yaqub Sheraz Yaqub Adrian McCann Per M. Ueland Per M. Ueland Knut Jørgen Labori Knut Jørgen Labori Johannes R. Hov Johannes R. Hov Johannes R. Hov |
| author_sort | Peder R. Braadland |
| collection | DOAJ |
| description | Background/AimsIt was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC.MethodWe measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC, collected before initiating neoadjuvant chemotherapy. The majority (61%) of the patients were treated with FOLFIRINOX. We used univariable and multivariable Cox proportional hazards regression to estimate the association between pre-treatment 3-IAA and overall survival.ResultsThe median serum 3-IAA concentration before chemotherapy was 290 (interquartile range 203–417) ng/mL. The unadjusted hazard ratio (HR) for pre-treatment log2(3-IAA) was 0.93, 95% confidence interval (CI) [0.74–1.16], p=0.52. When adjusting for age, ECOG, CA19-9 and tumor classification, the HR for log2(3-IAA) was 0.87, 95% CI [0.68–1.12], p=0.28.ConclusionOur findings suggest that the potentiating effect of 3-IAA observed in metastatic PDAC undergoing chemotherapy may not translate to borderline resectable or locally advanced PDAC. We recommend additional clinical validation of 3-IAA’s predictive value in different categories of PDAC before implementation attempts in human studies are initiated. |
| format | Article |
| id | doaj-art-654a6a2d67984b749cee2d51aeb1bbc4 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-654a6a2d67984b749cee2d51aeb1bbc42024-12-20T05:10:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-12-011410.3389/fonc.2024.14887491488749Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancerPeder R. Braadland0Peder R. Braadland1Ingvild Farnes2Ingvild Farnes3Elin H. Kure4Elin H. Kure5Sheraz Yaqub6Sheraz Yaqub7Adrian McCann8Per M. Ueland9Per M. Ueland10Knut Jørgen Labori11Knut Jørgen Labori12Johannes R. Hov13Johannes R. Hov14Johannes R. Hov15Research Institute of Internal Medicine and Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment of Natural Sciences and Environmental Health, University of South-Eastern Norway, Bø i Telemark, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, NorwayBEVITAL AS, Bergen, NorwayBEVITAL AS, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, NorwayResearch Institute of Internal Medicine and Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwaySection of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, NorwayBackground/AimsIt was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC.MethodWe measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC, collected before initiating neoadjuvant chemotherapy. The majority (61%) of the patients were treated with FOLFIRINOX. We used univariable and multivariable Cox proportional hazards regression to estimate the association between pre-treatment 3-IAA and overall survival.ResultsThe median serum 3-IAA concentration before chemotherapy was 290 (interquartile range 203–417) ng/mL. The unadjusted hazard ratio (HR) for pre-treatment log2(3-IAA) was 0.93, 95% confidence interval (CI) [0.74–1.16], p=0.52. When adjusting for age, ECOG, CA19-9 and tumor classification, the HR for log2(3-IAA) was 0.87, 95% CI [0.68–1.12], p=0.28.ConclusionOur findings suggest that the potentiating effect of 3-IAA observed in metastatic PDAC undergoing chemotherapy may not translate to borderline resectable or locally advanced PDAC. We recommend additional clinical validation of 3-IAA’s predictive value in different categories of PDAC before implementation attempts in human studies are initiated.https://www.frontiersin.org/articles/10.3389/fonc.2024.1488749/fullpancreatic adenocarcinomachemotherapy - oncologybiomarkersmicrobiomeindoles3-IAA |
| spellingShingle | Peder R. Braadland Peder R. Braadland Ingvild Farnes Ingvild Farnes Elin H. Kure Elin H. Kure Sheraz Yaqub Sheraz Yaqub Adrian McCann Per M. Ueland Per M. Ueland Knut Jørgen Labori Knut Jørgen Labori Johannes R. Hov Johannes R. Hov Johannes R. Hov Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer Frontiers in Oncology pancreatic adenocarcinoma chemotherapy - oncology biomarkers microbiome indoles 3-IAA |
| title | Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| title_full | Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| title_fullStr | Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| title_full_unstemmed | Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| title_short | Indole 3-acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| title_sort | indole 3 acetate and response to therapy in borderline resectable or locally advanced pancreatic cancer |
| topic | pancreatic adenocarcinoma chemotherapy - oncology biomarkers microbiome indoles 3-IAA |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1488749/full |
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