UBC Theses and Dissertations
Identifying clinical features and pre-analytical conditions that impact the performance of a blood-based microRNA biomarker (OrCaCept) for early detection of oral cancer Ametepe, Frederick Kofi
Oral squamous cell carcinoma (OSCC), the most prevalent subtype of head and neck cancer, has a poor survival rate of ~50% over 5 years due to frequent late stages of diagnosis and high recurrence rates. Serum-based biomarkers, such as miRNAs, represent a potential non-invasive mechanism for early detection to improve OSCC prognosis. Previously, we identified a serum-based miRNA signature - Oral Cancer Intercept (OrCaCept). This distinguishes individuals with OSCC from healthy, demographically-matched controls and detects recurrent disease before it is clinically evident with a sensitivity of 73.4% and specificity of 72.7%. To aid in the clinical adoption of OrCaCept, we must further investigate if any demographic, clinical, or pre-analytical features impact its performance. We hypothesize that certain factors may be associated with patients that exhibit an aberrant biomarker score. We assessed the expression levels of miR-125b and miR-342 in serum samples from 194 cancer patients and 135 healthy controls using qRT-PCR. Demographic and clinical features were statistically analyzed with ROC curves and one-and two-way ANOVA to identify factors that predict and correlate with the performance of each miRNA individually and the overall OrCaCept score. Skewed numbers towards Caucasian patients caused OrCaCept to perform better in them. OrCaCept worked well in the population with an elevated risk of OC and those with a recurrence rate expected to develop in 5 years. In addition, it also performed well in detecting cancers at all stages and locations in the oral cavity. Blood samples from 10 healthy volunteers were subjected to either extended blood clotting time or various serum storage times for pre-analytical features. Three miRNAs (miR-21-5p, miR-145-5p, and miR-342-3p) tested are relatively robust to minor disturbances in processing and storage conditions. However, in particular, one miRNA (miR-125b-5p) was more sensitive to abnormal conditions, with prolonged clotting at room temperature and warmer serum storage causing a significant decrease in fold-change. Understanding how these features influence OrCaCept performance will aid in identifying patients that most benefit from this test, creating a potential tool that clinicians could use to provide early intervention in OSCC recurrence and improve survival rates for this disease.
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