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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1797228833978449920 |
---|---|
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. |
first_indexed | 2024-04-24T15:02:59Z |
format | Article |
id | doaj.art-4453fa134c55430aa7f9edabd57de623 |
institution | Directory Open Access Journal |
issn | 2165-0497 |
language | English |
last_indexed | 2024-04-24T15:02:59Z |
publishDate | 2024-04-01 |
publisher | American Society for Microbiology |
record_format | Article |
series | Microbiology Spectrum |
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 |
work_keys_str_mv | AT jiali multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT yuzhang multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT yifancai multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT peizhuoyao multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT yiweijia multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT xinyuwei multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT chongdu multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer AT shuqunzhang multiomicsanalysiselucidatestherelationshipbetweenintratumormicrobiomeandhostimmuneheterogeneityinbreastcancer |