UBC Theses and Dissertations
Evaluation of circulating miRNA signatures as a blood test for the early detection of nasopharyngeal carcinoma Forder, Aisling
Nasopharyngeal carcinoma (NPC) is a head and neck cancer that lacks early clinical symptoms and is often diagnosed at later stages: existing studies characterizing circulating microRNAs (miRNAs) show potential as a noninvasive liquid biopsy for the early detection of NPC but there is little overlap among results. Thus, we aimed to identify a tumour-specific serum-based miRNA signature by eliminating miRNAs that have been previously reported to be impacted by hemolysis and accounting for circulating miRNAs that may be dysregulated due to inflammation in the tumour microenvironment using chronic rhinosinusitis (CRS) as a local inflammation control. Serum samples were obtained from 33 patients (NPC = 11, CRS = 12, healthy controls = 10) and 754 miRNAs profiled using RNA extracted from each sample. Eight miRNAs displayed differential expression in NPC vs. healthy controls but not in CRS vs. healthy controls (Benjamini-Hochberg corrected p < 0.05 and log2FC ≥ 2). Of these, four (miR-151b, miR-409-3p, miR-450a-5p, miR-941) were selected for further testing. Technical replication using RTqPCR (TaqMan Advanced miRNA Assays) was conducted using 30 of the original 33 samples (NPC = 10, CRS = 10, healthy controls = 10); however, a one-way ANOVA for each candidate was nonsignificant. Technical replication was then repeated using a different RTqPCR system (TaqMan miRNA Assays), with the addition of cel-miR-39 as an exogenous normalizer and miR-485-3p and miR-885-5p as two additional candidates based on previously reported differential expression in NPC in our lab. Ultimately, a one-way ANOVA for each candidate was also nonsignificant for this second replication attempt. In this pilot study we have demonstrated that a subset of circulating miRNAs is uniquely differentially expressed in NPC and that significant overlap exists between circulating miRNAs that are differentially expressed in NPC and in local inflammation; thus, accounting for this confounding variable in combination with the impact of hemolysis during sample processing is important to ensure tumour-specificity of candidate miRNAs. A limitation of the study is the small sample size, likely a major contributor to the nonsignificant technical replication, therefore future directions include the collection of a larger cohort to fully elucidate the potential circulating miRNA signature.
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