UBC Theses and Dissertations
Extracellular microRNAs as biomarkers for the detection of nasopharyngeal carcinoma Shoucair, Isrraa
Nasopharyngeal carcinoma (NPC) is a cancer of the upper region of the pharynx located behind the nose. Despite its low global incidence rate, this malignancy is endemic among primarily Chinese, South-East Asian, and Arctic descendants. microRNAs (miRNA) have been shown to be stable in circulation, with consistent aberrant expression profiles indicative of specific disease states – highlighting circulating miRNAs as attractive biomarkers. Preliminary testing for the feasibility of identifying a unique miRNA signature was conducted using Taqman Low Density Array (TLDA) cards. The profile of 754 miRNAs was assessed in serum samples from NPC patients, normal controls, and non-cancer oral/sinus inflammation patients. Differential expression of miR-151b, miR-450a-5p, miR-485-3p, and miR-885-5p were validated using qRT-PCR and assessed in matched NPC pre- and post-treatment serum samples. Additionally, extracellular vesicles (EVs) from NPC cell lines (HK1, Sune1) were collected via ultracentrifugation and the EV miRNA profiled via TLDA cards. 35 miRNAs were identified as significantly dysregulated in NPC serum compared to normal controls. Additionally, total of 46 miRNAs were identified as significantly dysregulated in non-cancer oral/sinus inflammation serum compared to normal controls. Cross-referencing these two lists, 12 miRNAs appear uniquely dysregulated only in NPC compared to controls. miR-485-3p was found to be downregulated in NPC serum, cells, and EVs. Moreover, expression of miR-485-3p, miR-151b, and miR-885-5p were significantly increased in NPC post-treatment samples. These results indicate the potential clinical utility and feasibility of establishing a simple, non-invasive, serum-based miRNA biomarker for the detection of NPC.
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