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The Ability of Serum miRNAs to Act as Biomarkers for the Oral Squamous Cell Carcinoma.Christopher DickmanCathie GarnisExperimental Medicine Research DayBackgroundOral Squamous Cell Carcinoma (OSCC) is the most common form of head and neck cancer

Poor survival rate due to rapid progression and frequent recurrence

Understanding molecular alterations in OSCC may lead to drug targets and biomarkersmiRNAsShort 22 base pair molecules of RNAResponsible for post-transcriptional genetic regulationKnown to play a role in many cancer processes

AimsWe aim to find miRNAs that are significantly different between the serum of individuals with oral cancer or carcinoma in situ (CIS) and healthy individuals that can be used as a biomarker for high risk lesionsMethodsSerum from 51 healthy individuals and 48 individuals with oral cancer or CIS were profiled for 742 miRNAs using RT-PCR47 additional control samples and 32 additional cancer/CIS samples were included in a validation set

HaemolysisAnalysis of serum miRNAs is made more difficult by the varying contribution of blood cell RNA to the serum

2 OptionsExclude samples with haemolysisExclude miRNAs affected by haemolysis

Data AnalysismiRNAs normalized to the expression of miR-23bCreation of a subset using general discriminant analysisSubset analysis was performed using a generalized linear model (logistic)Best subsets of 4,3 and 2 miRNAs were discoveredResults

ValidationSamples were run 8 per plate as opposed to one sample per two plates at ~1/8th the priceSamples are run in triplicateVariation among replicate increases in miRNAs with low expressionThere is difficulty in analyzing the data where all replicates have a different CT value Validation Results

Sources of Down-Regulated miRNAsMany of theses miRNAs are down regulated in cancer patients serum (miR-23a, 342-3p, 33a) what is their source?

Often its assumed cancer related miRNAs are released from the tumor

Immune system is known to be a large contributor to miRNA excretionConclusionsWe have identified candidates for a validation test of serum miRNA biomarkers for Oral CancerOngoing work must be preformed to determine what role overtraining plays in data analysisModelTraining AUCValidation AUC23a, 205, 33a 342-3p.91.7723a, 205, 33a.90.6223a, 205.83.6623a, 346.85NAAcknowledgementsSupervisorDr. Cathie Garnis

Committee MembersDr. Calum MacaulayDr. Catherine Poh

Garnis Lab MembersSara MacLellanRebecca TowleDanielle TruongJames Lawson