Association of tumor microbiome with survival in resected early-stage PDAC
ABSTRACT The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patie...
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| Language: | English |
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American Society for Microbiology
2025-03-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01229-24 |
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| author | Yixuan Meng Chan Wang Mykhaylo Usyk Soyoung Kwak Chengwei Peng Kenneth S. Hu Paul E. Oberstein Michelle Krogsgaard Huilin Li Richard B. Hayes Jiyoung Ahn |
| author_facet | Yixuan Meng Chan Wang Mykhaylo Usyk Soyoung Kwak Chengwei Peng Kenneth S. Hu Paul E. Oberstein Michelle Krogsgaard Huilin Li Richard B. Hayes Jiyoung Ahn |
| author_sort | Yixuan Meng |
| collection | DOAJ |
| description | ABSTRACT The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I–II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of Gammaproteobacteria, confirmed by extensive resampling, were significantly associated with OS (all Q < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26–3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4+ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent. |
| format | Article |
| id | doaj-art-52fe2bbe6e774ece8593d381eed3900a |
| institution | DOAJ |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj-art-52fe2bbe6e774ece8593d381eed3900a2025-08-20T02:56:23ZengAmerican Society for MicrobiologymSystems2379-50772025-03-0110310.1128/msystems.01229-24Association of tumor microbiome with survival in resected early-stage PDACYixuan Meng0Chan Wang1Mykhaylo Usyk2Soyoung Kwak3Chengwei Peng4Kenneth S. Hu5Paul E. Oberstein6Michelle Krogsgaard7Huilin Li8Richard B. Hayes9Jiyoung Ahn10Department of Population Health, NYU Grossman School of Medicine, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USANorthwestern University Feinberg School of Medicine, Chicago, Illinois, USADepartment of Radiation Oncology, NYU Grossman School of Medicine, New York, New York, USANYU Laura and Isaac Perlmutter Cancer Center, New York, New York, USANYU Laura and Isaac Perlmutter Cancer Center, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USADepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USAABSTRACT The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I–II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of Gammaproteobacteria, confirmed by extensive resampling, were significantly associated with OS (all Q < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26–3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4+ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent.https://journals.asm.org/doi/10.1128/msystems.01229-24tumor tissue microbiomeearly stagepancreatic cancersurvival |
| spellingShingle | Yixuan Meng Chan Wang Mykhaylo Usyk Soyoung Kwak Chengwei Peng Kenneth S. Hu Paul E. Oberstein Michelle Krogsgaard Huilin Li Richard B. Hayes Jiyoung Ahn Association of tumor microbiome with survival in resected early-stage PDAC mSystems tumor tissue microbiome early stage pancreatic cancer survival |
| title | Association of tumor microbiome with survival in resected early-stage PDAC |
| title_full | Association of tumor microbiome with survival in resected early-stage PDAC |
| title_fullStr | Association of tumor microbiome with survival in resected early-stage PDAC |
| title_full_unstemmed | Association of tumor microbiome with survival in resected early-stage PDAC |
| title_short | Association of tumor microbiome with survival in resected early-stage PDAC |
| title_sort | association of tumor microbiome with survival in resected early stage pdac |
| topic | tumor tissue microbiome early stage pancreatic cancer survival |
| url | https://journals.asm.org/doi/10.1128/msystems.01229-24 |
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