LE3 .A278 2022

2022

Coombs, Melanie

Acadia University

Bachelor of Science

Honours

Biology

Biology

The Canadian Cancer Society reports colorectal cancer (CRC) remains the second highest cause of cancer mortality in men and the third in women. Genetic mutations play a fundamental role in the formation and development of cancer. Mutation of several proto-oncogenes and tumor suppressor genes involved in key signal transduction pathways have proposed to play a crucial role in the initiation of cancer. In this study, a collection of colorectal cancer patient samples from The Cancer Genome Atlas (TCGA) Firehose legacy were analyzed. Clinical and mRNA expression data were attained from cBioportal. Gene expression of five genes of interest in colorectal cancer were analyzed, SRY-Box transcription factor-9 (SOX9), Kristen rat sarcoma virus (KRAS), adenomatous polyposis coli (APC), tumor protein gene 53 (TP53), and SMAD family member 4 (SMAD4). Sample data were divided based on clinical differences in survival status, sex, and progression stage. The gene expression of each gene of interest were compared to identify any significant differences in expression between different clinical groups. Tumor suppressor APC displayed a significant difference in mRNA expression between male and female colorectal (CRC) patient groups. Tumor suppressor SMAD4 was significantly downregulated between stage I and IV CRC patient samples and stage II and IV CRC patient samples. Downregulation of APC in males supports the high incidence of CRC in males. APC’s involvement in the WNT signaling pathway suggests this pathway is likely disrupted in CRC and play a significant role in the CRC development and progression. SMAD4’s implication in TGF-β suggests a disruption of this cellular signaling pathway. WNT and TGF-β signaling pathways may therefore be of interest for future research to better understand cancer at a genetic and cellular level. APC and SMAD4 may provide useful intracellular therapeutic targets, or act as potential biomarkers for CRC.

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https://scholar.acadiau.ca/islandora/object/theses:3776