Racial disparities in metastatic colorectal cancer outcomes revealed by tumor microbiome and transcriptome analysis with bevacizumab treatment

Lei Feng; Rui Wang; Qian Zhao; Jun Wang; Gang Luo; Chongwen Xu

doi:10.3389/fphar.2023.1320028

Racial disparities in metastatic colorectal cancer outcomes revealed by tumor microbiome and transcriptome analysis with bevacizumab treatment

Front Pharmacol. 2024 Jan 31:14:1320028. doi: 10.3389/fphar.2023.1320028. eCollection 2023.

Authors

Lei Feng^{1

2}, Rui Wang³, Qian Zhao¹, Jun Wang⁴, Gang Luo^{1

2}, Chongwen Xu¹

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Surgical Oncology, Hanzhong People's Hospital, Hanzhong, Shaanxi, China.
³ Department of Thoracic Surgery, Cancer Centre, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁴ Tongji Hospital Tongji Medical College of HUST, Wuhan, China.

Abstract

Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored. Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing. Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively. Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC's pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.

Keywords: bevacizumab; intratumoral microbiome; mCRC; multi-omics; racial variations; transcriptomics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The research leading to these results mainly received funding from the Basic Natural Science Research Program of Shaanxi Province 2021JQ-386, 2021JQ-405, and 2022JM-610 (Referred to CX), funding from the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, XJTU1AF-CRF-2020-020 (Referred to CX). This study also received funding from Key Research and Development Program of Shaanxi Province, 2022SF-159 (Referred to CX), National Natural Science Foundation of China, No. 82103568 (Referred to CX).