Tumor-associated microbiome features of metastatic colorectal cancer and clinical implications

Ho Jung An; Mira A Partha; HoJoon Lee; Billy T Lau; Dmitri S Pavlichin; Alison Almeda; Anna C Hooker; Giwon Shin; Hanlee P Ji

doi:10.3389/fonc.2023.1310054

Tumor-associated microbiome features of metastatic colorectal cancer and clinical implications

Front Oncol. 2024 Jan 18:13:1310054. doi: 10.3389/fonc.2023.1310054. eCollection 2023.

Authors

Ho Jung An^{1

2}, Mira A Partha³, HoJoon Lee², Billy T Lau², Dmitri S Pavlichin², Alison Almeda², Anna C Hooker², Giwon Shin², Hanlee P Ji^{2

3}

Affiliations

¹ Department of Medical Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
² Division of Oncology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.
³ Department of Electrical Engineering, Stanford University, Palo Alto, CA, United States.

Abstract

Background: Colon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of patients with metastatic CRC and determined the clinical implications.

Materials and methods: We enrolled 133 patients with metastatic CRC at St. Vincent Hospital in Korea. The V3-V4 regions of the 16S rRNA gene from the tumor DNA were amplified, sequenced on an Illumina MiSeq, and analyzed using the DADA2 package.

Results: After excluding samples that retained <5% of the total reads after merging, 120 samples were analyzed. The median age of patients was 63 years (range, 34-82 years), and 76 patients (63.3%) were male. The primary cancer sites were the right colon (27.5%), left colon (30.8%), and rectum (41.7%). All subjects received 5-fluouracil-based systemic chemotherapy. After removing genera with <1% of the total reads in each patient, 523 genera were identified. Rectal origin, high CEA level (≥10 ng/mL), and presence of lung metastasis showed higher richness. Survival analysis revealed that the presence of Prevotella (p = 0.052), Fusobacterium (p = 0.002), Selenomonas (p<0.001), Fretibacterium (p = 0.001), Porphyromonas (p = 0.007), Peptostreptococcus (p = 0.002), and Leptotrichia (p = 0.003) were associated with short overall survival (OS, <24 months), while the presence of Sphingomonas was associated with long OS (p = 0.070). From the multivariate analysis, the presence of Selenomonas (hazard ratio [HR], 6.35; 95% confidence interval [CI], 2.38-16.97; p<0.001) was associated with poor prognosis along with high CEA level.

Conclusion: Tumor microbiome features may be useful prognostic biomarkers for metastatic CRC.

Keywords: adenocarcinoma; colon; metastasis; rectum; tissue microbiome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Clayville Foundation, Fund for Innovation in Cancer Informatics, Catholic Medical Center Research Foundation in the program year of 2023, and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. RS-2023-00249672).