Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer

ABSTRACTResearch has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for...

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Main Authors: Jia Li, Yu Zhang, Yifan Cai, Peizhuo Yao, Yiwei Jia, Xinyu Wei, Chong Du, Shuqun Zhang
Format: Article
Language:English
Published: American Society for Microbiology 2024-04-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.04104-23
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author Jia Li
Yu Zhang
Yifan Cai
Peizhuo Yao
Yiwei Jia
Xinyu Wei
Chong Du
Shuqun Zhang
author_facet Jia Li
Yu Zhang
Yifan Cai
Peizhuo Yao
Yiwei Jia
Xinyu Wei
Chong Du
Shuqun Zhang
author_sort Jia Li
collection DOAJ
description ABSTRACTResearch has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for potential prognosis prediction factors and treatment targets. The clinical information, microbiome data, transcriptomics data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) patients were obtained from Kraken-TCGA-Raw-Data and TCGA portal. The core tumor-infiltrating immune cell was identified using univariate Cox regression analysis. Based on consensus clustering analysis, BC patients were categorized into two immune subtypes, referred to as immune-enriched and immune-deficient subtypes. The immune-enriched subtype, characterized by higher levels of immune infiltration of CD8+ T and macrophage M1 cells, demonstrated a more favorable prognosis. Furthermore, significant differences in alpha-diversity and beta-diversity were observed between the two immune subtypes, and the least discriminant analysis effect size method identified 33 types of IRIMs. An intratumor microbiome-based prognostic signature consisting of four prognostic IRIMs (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania) was constructed using the Cox proportional-hazard model, and it had great prognostic value. The prognostic IRIMs were correlated with immune gene expression and the sensitivity of chemotherapy drugs, specifically tamoxifen and docetaxel. In conclusion, our research has successfully identified two distinct immune subtypes in BC, which exhibit contrasting prognoses and possess unique epigenetic and intratumor microbiomes. The critical IRIMs were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in BC. Consequently, this study has identified potential IRIMs as biomarkers, providing a novel therapeutic approach for treating BC.IMPORTANCERecent research has substantiated the presence of the intratumor microbiome in tumor immune microenvironment, which could influence tumor occurrence and progression, as well as provide new opportunities for cancer diagnosis and treatment. This study identified the critical immune-related intratumor microbiome (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania), which were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in breast cancer and might be the novel target to regulate immunotherapy in BC.
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spelling doaj.art-4453fa134c55430aa7f9edabd57de6232024-04-02T14:16:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-04-0112410.1128/spectrum.04104-23Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancerJia Li0Yu Zhang1Yifan Cai2Peizhuo Yao3Yiwei Jia4Xinyu Wei5Chong Du6Shuqun Zhang7Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi, ChinaABSTRACTResearch has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for potential prognosis prediction factors and treatment targets. The clinical information, microbiome data, transcriptomics data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) patients were obtained from Kraken-TCGA-Raw-Data and TCGA portal. The core tumor-infiltrating immune cell was identified using univariate Cox regression analysis. Based on consensus clustering analysis, BC patients were categorized into two immune subtypes, referred to as immune-enriched and immune-deficient subtypes. The immune-enriched subtype, characterized by higher levels of immune infiltration of CD8+ T and macrophage M1 cells, demonstrated a more favorable prognosis. Furthermore, significant differences in alpha-diversity and beta-diversity were observed between the two immune subtypes, and the least discriminant analysis effect size method identified 33 types of IRIMs. An intratumor microbiome-based prognostic signature consisting of four prognostic IRIMs (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania) was constructed using the Cox proportional-hazard model, and it had great prognostic value. The prognostic IRIMs were correlated with immune gene expression and the sensitivity of chemotherapy drugs, specifically tamoxifen and docetaxel. In conclusion, our research has successfully identified two distinct immune subtypes in BC, which exhibit contrasting prognoses and possess unique epigenetic and intratumor microbiomes. The critical IRIMs were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in BC. Consequently, this study has identified potential IRIMs as biomarkers, providing a novel therapeutic approach for treating BC.IMPORTANCERecent research has substantiated the presence of the intratumor microbiome in tumor immune microenvironment, which could influence tumor occurrence and progression, as well as provide new opportunities for cancer diagnosis and treatment. This study identified the critical immune-related intratumor microbiome (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania), which were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in breast cancer and might be the novel target to regulate immunotherapy in BC.https://journals.asm.org/doi/10.1128/spectrum.04104-23intratumor microbiomebreast cancertumor immune microenvironmentimmunotherapyprognostic factors
spellingShingle Jia Li
Yu Zhang
Yifan Cai
Peizhuo Yao
Yiwei Jia
Xinyu Wei
Chong Du
Shuqun Zhang
Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
Microbiology Spectrum
intratumor microbiome
breast cancer
tumor immune microenvironment
immunotherapy
prognostic factors
title Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
title_full Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
title_fullStr Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
title_full_unstemmed Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
title_short Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
title_sort multi omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer
topic intratumor microbiome
breast cancer
tumor immune microenvironment
immunotherapy
prognostic factors
url https://journals.asm.org/doi/10.1128/spectrum.04104-23
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