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Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients...

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Autores principales: Nakazawa, Nobuhiro, Yokobori, Takehiko, Sohda, Makoto, Hosoi, Nobuhiro, Watanabe, Takayoshi, Shimoda, Yuki, Ide, Munenori, Sano, Akihiko, Sakai, Makoto, Erkhem-Ochir, Bilguun, Ogawa, Hiroomi, Shirabe, Ken, Saeki, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380503/
https://www.ncbi.nlm.nih.gov/pubmed/37511547
http://dx.doi.org/10.3390/ijms241411790
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author Nakazawa, Nobuhiro
Yokobori, Takehiko
Sohda, Makoto
Hosoi, Nobuhiro
Watanabe, Takayoshi
Shimoda, Yuki
Ide, Munenori
Sano, Akihiko
Sakai, Makoto
Erkhem-Ochir, Bilguun
Ogawa, Hiroomi
Shirabe, Ken
Saeki, Hiroshi
author_facet Nakazawa, Nobuhiro
Yokobori, Takehiko
Sohda, Makoto
Hosoi, Nobuhiro
Watanabe, Takayoshi
Shimoda, Yuki
Ide, Munenori
Sano, Akihiko
Sakai, Makoto
Erkhem-Ochir, Bilguun
Ogawa, Hiroomi
Shirabe, Ken
Saeki, Hiroshi
author_sort Nakazawa, Nobuhiro
collection PubMed
description Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), wnt3a, and E-cadherin (epithelial–mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling (p = 0.0028) and decreased E-cadherin expression (p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS (p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively (p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-β signaling, and epithelial–mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab.
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spelling pubmed-103805032023-07-29 Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity Nakazawa, Nobuhiro Yokobori, Takehiko Sohda, Makoto Hosoi, Nobuhiro Watanabe, Takayoshi Shimoda, Yuki Ide, Munenori Sano, Akihiko Sakai, Makoto Erkhem-Ochir, Bilguun Ogawa, Hiroomi Shirabe, Ken Saeki, Hiroshi Int J Mol Sci Article Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), wnt3a, and E-cadherin (epithelial–mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling (p = 0.0028) and decreased E-cadherin expression (p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS (p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively (p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-β signaling, and epithelial–mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab. MDPI 2023-07-22 /pmc/articles/PMC10380503/ /pubmed/37511547 http://dx.doi.org/10.3390/ijms241411790 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nakazawa, Nobuhiro
Yokobori, Takehiko
Sohda, Makoto
Hosoi, Nobuhiro
Watanabe, Takayoshi
Shimoda, Yuki
Ide, Munenori
Sano, Akihiko
Sakai, Makoto
Erkhem-Ochir, Bilguun
Ogawa, Hiroomi
Shirabe, Ken
Saeki, Hiroshi
Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title_full Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title_fullStr Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title_full_unstemmed Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title_short Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity
title_sort significance of lipopolysaccharides in gastric cancer and their potential as a biomarker for nivolumab sensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380503/
https://www.ncbi.nlm.nih.gov/pubmed/37511547
http://dx.doi.org/10.3390/ijms241411790
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