B0092 - Increased Primary Tumor Sutterella Bacterial RNAseq Signatures Are Associated With Increased M2 Macrophage Abundance and Worse Overall Survival in Rectal Adenocarcinoma

Saif Zaman, MD¹, George Chen, MD², Daniel Segarra, MD³, Ankoor Patel, MD⁴, Petr Protiva, MD^2
1Yale New Haven Hospital, New Haven, CT; ²Yale University School of Medicine, New Haven, CT; ³USF Internal Medicine, Tampa, FL; ⁴Rutgers Robert Wood Johnson, New Brunswick, NJ

Introduction: Although gut microbiome dysbiosis has been implicated in colorectal cancer, the role of intratumor microbiome in carcinogenesis has not been studied extensively. We aimed to identify intratumor bacterial genera that are significantly correlated with M2 tumor-associated macrophage (TAM) abundance in rectal adenocarcinoma and analyze associations of those bacterial genera with overall survival.

Methods: RNA sequencing (RNA-seq) data for 1206 bacterial genera was procured as described by Poore et al. and used to calculate average log2 counts per million for each bacterial genus. Intratumor M2 TAM abundance was first estimated by quanTIseq, an RNAseq deconvolution algorithm, and verified by CIBERSORT, another RNA-seq-based in silico approach for characterizing cell subsets in tumor samples. Pearson correlation analysis of intratumor abundance of each bacterial genus and M2 TAM was conducted. Bonferroni correction was used for multiple comparisons correction. Next, for bacterial genera correlated with M2 TAM abundance, we analyzed their associations with overall survival in rectal adenocarcinoma using clinical data from The Cancer Genome Atlas Rectal Adenocarcinoma database. Only patients with primary tumor sites in the rectum (n=158) were included for analysis. Relative hazard ratios (HRs) for overall survival were estimated with cox proportional hazards models using the lifelines python package, with p-value threshold set at < 0.05 for independent t-tests.

Results: Among 1206 bacterial genera with RNA-seq data, Sutterella was the only bacterial genus significantly positively correlated with M2 TAM abundance estimated via the quantiSeq method after Bonferroni correction (Pearson correlation coefficient=0.38; p=6.7E-7) (Figure 1A). This significant correlation was replicated in correlation analysis using M2 TAM abundance estimated via the CIBERSORT method (Pearson correlation coefficient=0.17; p=0.03) (Figure 1B). In 151 patients with primary rectal adenocarcinoma, intratumor Sutterella abundance was significantly associated with worse overall survival (HR 1.45; p=0.02) after adjusting for age, sex, and tumor stage (Table 1).

Discussion: This is the first study to identify associations of intratumor microbiome with TAMs in rectal adenocarcinoma. We found Sutterella abundance to be associated with M2 TAM abundance and poor overall survival, highlighting the need for further investigation of mechanistic pathways linking intratumor microbiome and carcinogenesis.



Disclosures:


Saif Zaman, MD¹, George Chen, MD², Daniel Segarra, MD³, Ankoor Patel, MD⁴, Petr Protiva, MD². B0092 - Increased Primary Tumor Sutterella Bacterial RNAseq Signatures Are Associated With Increased M2 Macrophage Abundance and Worse Overall Survival in Rectal Adenocarcinoma, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.