E0094 - High Intratumoral Hepatovirus Abundance in Colon Adenocarcinoma Is Associated With Worse Overall Survival and Increased Intratumoral CD8+ T-Cell Infiltration

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

Introduction: Hepatovirus infection is positively associated with colon adenocarcinoma (COAD) risk, but its role in COAD tumorigenesis remains unclear. We aimed to investigate whether intratumoral hepatovirus abundance in COAD is independently associated with both overall survival and intratumoral immune cell infiltrate.

Methods: We included patients with primary COAD and hepatovirus RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) COAD database. RNA-seq data procured as described previously by Poore et al. (Nature, 2020) was used to estimate intratumoral hepatovirus abundance by calculating the average log2 of transcripts per million for each patient. Demographic and clinical data, including age, sex, and tumor stage, were downloaded from TCGA-COAD using cBioPortal.org. Relative hazard ratios (HRs) for overall survival were estimated with Cox proportional hazards model using the lifelines python package. A significance threshold of p≤0.05 was used for independent t-tests. Intratumoral immune cell abundance was estimated via the quanTIseq, a devolution algorithm described previously by Finotello et al. (Genome Medicine, 2019). Spearman correlation analysis was then used to assess the association between intratumoral hepatovirus and immune cell abundance.

Results: In 432 patients with primary COAD, intratumoral hepatovirus abundance was significantly associated with shorter overall survival (HR 1.25; p=0.05) in Cox proportional hazards model adjusted for age, sex, and tumor stage (Table 1). Next, we sought to analyze associations of hepatovirus abundance with 10 immune cell types. Spearman correlation analysis showed intratumoral hepatovirus abundance was significantly positively correlated with intratumoral CD8+ T cell infiltration (correlation coefficient=0.11; p=0.02) but not with B cells, M1 macrophages, M2 macrophages, myeloid dendritic cells, monocytes, neutrophils, natural killer cells, CD4+ T cells, or regulatory T cells.

Discussion: To our knowledge, this is the first study to identify an association between intratumoral hepatovirus abundance and overall survival in COAD. We also found a significant correlation between intratumoral hepatovirus and CD8+ T cell abundance, highlighting the potential role of hepatovirus in immune and inflammatory pathways regulating COAD carcinogenesis.


Disclosures:


George Chen, MD¹, Saif Zaman, MD², Daniel Segarra, MD³, Ankoor Patel, MD⁴, Petr Protiva, MD¹. E0094 - High Intratumoral Hepatovirus Abundance in Colon Adenocarcinoma Is Associated With Worse Overall Survival and Increased Intratumoral CD8+ T-Cell Infiltration, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.