A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer.

Area of Science:

• Genomics
• Bioinformatics
• Cancer Biology

Background:

• Colorectal cancer (CRC) exhibits significant racial disparities, with Black/African Americans (AA) experiencing higher incidence and mortality rates compared to White patients.
• The underlying biological mechanisms contributing to these disparities remain largely unknown, hindering targeted treatment strategies.
• Existing research is limited by a lack of studies with sufficient sample sizes of Black/AA cohorts.

Purpose of the Study:

• To investigate the role of gene expression differences in the racial disparities observed in colorectal cancer (CRC) between Black/AA and White patient cohorts.
• To identify specific genes and pathways associated with these disparities using a systems biology and bioinformatics approach.
• To provide a foundation for developing precision medicine strategies tailored to address CRC racial disparities.

Main Methods:

• Transcriptomic data from Black/AA and White CRC patient cohorts were analyzed using bioinformatics and systems biology methods.
• Kaplan-Meier survival analysis was performed across colorectal cancer signal transduction networks (STN) to identify cohort-specific survival associations.
• Differential gene expression analysis (DESeq2), multivariable regression, and PROGENy pathway analysis were employed.

Main Results:

• Identification of novel prognostic genes specific to each patient cohort.
• Discovery of 176 differentially expressed genes between Black/AA and White CRC patient cohorts.
• Specific associations between patient cohorts and signal transduction network (STN) survival were elucidated, highlighting distinct biological behaviors.

Conclusions:

• This study reveals significant, novel differences in gene expression between Black/AA and White patients with colorectal cancer (CRC).
• These findings provide critical insights into the systems-level biological factors potentially driving racial disparities in CRC.
• The identified disparity-associated genes and pathways offer a tangible starting point for guiding precision medicine approaches to mitigate CRC racial disparities.