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Colorectal

Colorectal Parallel Session

21: Stage-Specific Analysis of Racial Disparities in Colon Cancer Gene Expression Profiles

Friday, March 22, 2024

10:32am – 10:42am ET

Location: C101

Abstract Presenter(s)

Mohamad El Moheb, MD

General Surgery Resident
University of Virginia
Charlottesville, Virginia, United States

Submitter(s)

Mohamad El Moheb, MD

General Surgery Resident
University of Virginia
Charlottesville, Virginia, United States

Author(s)

CS

Chengli Shen, MS, PhD

Research Scientist
University of Virginia, United States
Susan J. Kim, MD (she/her/hers)

Post-doctoral Research Fellow
University of Virginia
Charlottesville, Virginia, United States
HZ

Hongji Zhang, Md PhD

Assistant Professor
University of Virginia, United States
RW

Russell Witt, MD

Assistant Professor in Surgery
University of Virginia, United States
Allan Tsung, MD

Chair of Department of Surgery, Professor of Surgery, Principal Investigator
University of Virginia, United States

Disclosure(s):

Mohamad El Moheb, MD: No financial relationships to disclose

Susan J. Kim, MD: No financial relationships to disclose

Introduction: African Americans (AA) with colon cancer consistently exhibit worse overall survival compared to White patients at every stage. No study has explored stage-specific transcriptional variations that might account for these disparities. Herein, we sought to evaluate the stage-specific differences in the transcriptional profiles between AA and White patients with colon cancer.

Methods: Colon cancer patients from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset were categorized into localized (I-II), regional (III), and distant (IV) stages. Patients with multiple samples or missing race data were excluded. For each stage, AA and White patients were compared by sex, age, tumor location, and prior malignancy. Propensity Score Matching was used for imbalanced groups. Differential expression of protein-coding genes in primary tumors between AA and White patients was assessed per stage, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set enrichment analysis. All p-values were adjusted for multiple comparisons.

Results:

Of 247 analyzed patients, 128 had localized disease (104 White, 24 AA), 81 had regional (60 White, 21 AA), and 38 had distant disease (27 White, 11 AA). The mean (standard deviation) age was 64.9 (13.3) years, and 50.7% were male. 675 protein-coding genes were differentially expressed in AA with localized disease, 163 with regional disease, and 289 with distant disease compared to White patients. Nine genes were differentially expressed in all groups: F8A1, ULK4, POLR2J3, PRSS21, STK36, RSKR, POLR2J2, LRRC37A, RAMACL, MUC16, and STRADA (Figure 1). PRSS21, known to inhibit ovarian tumor metastasis by antagonizing proangiogenic proteins, was under-expressed in AA with locoregional disease but overexpressed in distant disease. AA patients with localized disease had downregulation of immune modulator genes including IFN-gamma, CXCL5, CXCL6, CXCL8, and CXCL10 (p< 0.05). Pathway enrichment analysis showed downregulation of the IL-17 signaling pathway, known to induce neutrophil mobilization and activation, in AA compared to White patients.

Conclusions:

This study revealed significant transcriptional differences for all disease stages between AA and White colon cancer patients. Nine genes were consistently differentially expressed in all stages, including PRSS21, downregulated in locoregional stages but overexpressed post-metastasis. Downregulation of the IL-17 signaling pathway in AA with localized disease suggests a potential dampening of immune responses. Further validation with an external cohort is warranted.

Learning Objectives:

Upon completion, participants will be able to describe the variation patterns in the gene expression profiles of White and African American patients at each disease stage.
Upon completion, participants will be able to recognize the downregulation of immune genes and the IL-17 pathway in localized colon cancer among African American patients compared to White patients.
Upon completion, participants will be able to explain how gene expression differences between African American and White colon cancer tumors potentially affect survival disparities.