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Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer
Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219162/ https://www.ncbi.nlm.nih.gov/pubmed/35587155 http://dx.doi.org/10.1093/jncics/pkac039 |
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author | Guenther, Michael Gil, Lina Surendran, Sai Agash Palm, Melanie Alexandra Heinemann, Volker von Bergwelt-Baildon, Michael Mayerle, Julia Engel, Jutta Werner, Jens Boeck, Stefan Ormanns, Steffen |
author_facet | Guenther, Michael Gil, Lina Surendran, Sai Agash Palm, Melanie Alexandra Heinemann, Volker von Bergwelt-Baildon, Michael Mayerle, Julia Engel, Jutta Werner, Jens Boeck, Stefan Ormanns, Steffen |
author_sort | Guenther, Michael |
collection | PubMed |
description | Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with aGC or without aGC adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease-free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22 to 2.49; log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23 to 2.57; log-rank P = .001) but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as a negative predictor for aGC efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance. |
format | Online Article Text |
id | pubmed-9219162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92191622022-06-28 Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer Guenther, Michael Gil, Lina Surendran, Sai Agash Palm, Melanie Alexandra Heinemann, Volker von Bergwelt-Baildon, Michael Mayerle, Julia Engel, Jutta Werner, Jens Boeck, Stefan Ormanns, Steffen JNCI Cancer Spectr Brief Communications Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with aGC or without aGC adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease-free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22 to 2.49; log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23 to 2.57; log-rank P = .001) but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as a negative predictor for aGC efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance. Oxford University Press 2022-05-19 /pmc/articles/PMC9219162/ /pubmed/35587155 http://dx.doi.org/10.1093/jncics/pkac039 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Brief Communications Guenther, Michael Gil, Lina Surendran, Sai Agash Palm, Melanie Alexandra Heinemann, Volker von Bergwelt-Baildon, Michael Mayerle, Julia Engel, Jutta Werner, Jens Boeck, Stefan Ormanns, Steffen Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title | Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title_full | Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title_fullStr | Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title_full_unstemmed | Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title_short | Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer |
title_sort | bacterial lipopolysaccharide as a negative predictor of adjuvant gemcitabine efficacy in pancreatic cancer |
topic | Brief Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219162/ https://www.ncbi.nlm.nih.gov/pubmed/35587155 http://dx.doi.org/10.1093/jncics/pkac039 |
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