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Zanif, Umaimah Nikhat

University of British Columbia

Background/Objectives: Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but the mechanisms underlying these associations remain poorly understood. Our primary objective was to explore the association of these factors with expression of two biomarkers in CRC, SPARC and PD-L1, for which lower and higher levels of expression, respectively, have been associated with poorer CRC prognosis. Methods: Participants were drawn from the British Columbia Generations Project (BCGP), who at time of recruitment, provided data on various demographic, health history, and lifestyle factors. Formalin-fixed paraffin-embedded blocks were obtained for 49 incident BCGP CRC cases and used to create tissue microarrays. Slides created from the microarrays were stained with SPARC and PD-L1 antibodies and analyzed to calculate H-scores as measures of expression in both epithelial and non-epithelial tissues. Linear regression analyses were used to evaluate associations between the various factors and ln-transformed H-scores. Results: In CRC tumour epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression (p=0.05); a similar though non-significant, association was observed in non-epithelial tumour tissue. Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue (p=0.04); a similar effect was not observed in tumour epithelium. Higher stage was associated with a 0.74-fold lower level of non-epithelial tumour SPARC expression (p=0.04). A similar non-significant effect was observed in tumour epithelium. PD-L1 expression in tumour epithelium was 2.84-fold greater among females (p=0.005). A similar non-significant effect was observed in tumour non-epithelial tissue. History of CRC screening was statistically significantly associated with 2-fold greater levels of PD-L1 expression in tumour epithelial and non-epithelial tissues (p=0.04). Conclusion: Associations of SPARC expression with smoking, income, and stage, but not PD-L1 expression with biological sex and history of CRC screening, were consistent with the previously established associations of these factors with CRC prognosis. Larger scale studies with prognostic data are needed, but our results suggest that differences in expression of SPARC may contribute to the previously observed impacts of factors on CRC prognosis. However, additional work to understand the role of PD-L1 in CRC prognosis is needed.

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2024-03-18

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87590

Interdisciplinary Oncology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/