Stage and location related intratumoral microbiota are associated with patient prognosis and immune infiltration in colorectal cancer-Reference-Cited by-同舟云学术

Stage and location related intratumoral microbiota are associated with patient prognosis and immune infiltration in colorectal cancer

Published:2023-04-20 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Zhao Mengyu¹,Zhang Xiang²,Wang Fuhao²,Hu Xiaoyu²,Xue Zhuang²,Chen Ming²,Yue Jinbo¹

Affiliation:

1. Cheeloo College of Medicine, Shandong University

2. Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences

Abstract

Abstract Purpose: The colorectal intratumoral microbiome and its association with immune infiltration remain poorly characterized. Our study aims to investigate the relationship between intratumoral microbiota with immune infiltration, patient prognosis, and potential signal pathways. Methods: We collected biopsy samples of tumor and paracancerous tissue from 92 patients with colorectal cancer (CRC), and acquired microbiota profiling using 16S rRNA sequencing. Meanwhile, the immune markers including CD8, FOXP3, CD163, PD-1 and PD-L1 were stained by immunohistochemistry (IHC) to identify the immune infiltration in tumors. Furthermore, we used The Cancer Genome Atlas databases to conduct analysis on intratumoral flora and patient survival, tumor gene expression profile and potential downstream pathways. Results: We discovered that the β-diversity of bacterial composition differed considerably by CRC stage (early vs.advanced stage, P = 0.049) and location (left vs. right colon, P= 0.04). Stage-related flora cluster (Porphyromonas, Lachnoclostridium, Bacteroides, Aggregatibacter, and Hungatella) were associated with poor prognosis in CRC patients (HR=1.79, P=0.015). By IHC staining, we found that expression of PD-1 and FOXP3 was significantly reduced at low abundance of stage-related bacterial cluster (P<0.05). Besides, tumor-location related flora cluster (Bacteroides and Blautia) were associated with good prognosis in CRC patients (HR=0.52, P=0.011). Expression of CD163 was decreased at high abundance of location-related bacterial cluster (P<0.05). Furthermore, we identified probable pathways connected to three distinct genera (Blautia, Hungatella, and Bacteroides). Conclusion: Our study elucidates the relationships among intratumoral microbiota, immune infiltration, patient prognosis, and potential signal pathways, thereby providing new data for future intratumoral microbiota research.

Publisher

Research Square Platform LLC

Reference47 articles.

1. 'The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients';Boleij Annemarie;Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America,2015

2. Bolyen, Evan, Jai Ram Rideout, Matthew R. Dillon, Nicholas A. Bokulich, Christian C. Abnet, Gabriel A. Al-Ghalith, Harriet Alexander, Eric J. Alm, Manimozhiyan Arumugam, Francesco Asnicar, Yang Bai, Jordan E. Bisanz, Kyle Bittinger, Asker Brejnrod, Colin J. Brislawn, C. Titus Brown, Benjamin J. Callahan, Andrés Mauricio Caraballo-Rodríguez, John Chase, Emily K. Cope, Ricardo Da Silva, Christian Diener, Pieter C. Dorrestein, Gavin M. Douglas, Daniel M. Durall, Claire Duvallet, Christian F. Edwardson, Madeleine Ernst, Mehrbod Estaki, Jennifer Fouquier, Julia M. Gauglitz, Sean M. Gibbons, Deanna L. Gibson, Antonio Gonzalez, Kestrel Gorlick, Jiarong Guo, Benjamin Hillmann, Susan Holmes, Hannes Holste, Curtis Huttenhower, Gavin A. Huttley, Stefan Janssen, Alan K. Jarmusch, Lingjing Jiang, Benjamin D. Kaehler, Kyo Bin Kang, Christopher R. Keefe, Paul Keim, Scott T. Kelley, Dan Knights, Irina Koester, Tomasz Kosciolek, Jorden Kreps, Morgan G. I. Langille, Joslynn Lee, Ruth Ley, Yong-Xin Liu, Erikka Loftfield, Catherine Lozupone, Massoud Maher, Clarisse Marotz, Bryan D. Martin, Daniel McDonald, Lauren J. McIver, Alexey V. Melnik, Jessica L. Metcalf, Sydney C. Morgan, Jamie T. Morton, Ahmad Turan Naimey, Jose A. Navas-Molina, Louis Felix Nothias, Stephanie B. Orchanian, Talima Pearson, Samuel L. Peoples, Daniel Petras, Mary Lai Preuss, Elmar Pruesse, Lasse Buur Rasmussen, Adam Rivers, Michael S. Robeson, Patrick Rosenthal, Nicola Segata, Michael Shaffer, Arron Shiffer, Rashmi Sinha, Se Jin Song, John R. Spear, Austin D. Swafford, Luke R. Thompson, Pedro J. Torres, Pauline Trinh, Anupriya Tripathi, Peter J. Turnbaugh, Sabah Ul-Hasan, Justin J. J. van der Hooft, Fernando Vargas, Yoshiki Vázquez-Baeza, Emily Vogtmann, Max von Hippel, William Walters, Yunhu Wan, Mingxun Wang, Jonathan Warren, Kyle C. Weber, Charles H. D. Williamson, Amy D. Willis, Zhenjiang Zech Xu, Jesse R. Zaneveld, Yilong Zhang, Qiyun Zhu, Rob Knight, and J. Gregory Caporaso. 2019. 'Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2', Nature Biotechnology, 37: 852 – 57.

3. Callahan, Benjamin J., Paul J. McMurdie, Michael J. Rosen, Andrew W. Han, Amy Jo A. Johnson, and Susan P. Holmes. 2016. 'DADA2: High-resolution sample inference from Illumina amplicon data', Nature Methods, 13: 581 – 83.

4. 'Influence of gut and intratumoral microbiota on the immune microenvironment and anti-cancer therapy';Chen Yun;Pharmacological Research,2021

5. 'The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation';Cheng WT;Malays J Med Sci,2020