1. Christopher Dickman Cathie Garnis Experimental Medicine Research Day
The Ability of Serum miRNAs to Act as Biomarkers for the Oral Squamous Cell Carcinoma.
Christopher Dickman
Cathie Garnis
Experimental Medicine Research Day

2. Background
Oral 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 biomarkers

3. miRNAs Short 22 base pair molecules of RNA
Responsible for post-transcriptional genetic regulation
Known to play a role in many cancer processes

4. Aim s
We 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 lesions

5. Methods
Serum from 51 healthy individuals and 48 individuals with oral cancer or CIS were profiled for 742 miRNAs using RT-PCR
47 additional control samples and 32 additional cancer/CIS samples were included in a validation set

6. Haemolysis
Analysis of serum miRNAs is made more difficult by the varying contribution of blood cell RNA to the serum
2 Options
Exclude samples with haemolysis
Exclude miRNAs affected by haemolysis

7. Data Analysis miRNAs normalized to the expression of miR-23b
Creation of a subset using general discriminant analysis
Subset analysis was performed using a generalized linear model (logistic)
Best subsets of 4,3 and 2 miRNAs were discovered

8. Results

9. Validation
Samples were run 8 per plate as opposed to one sample per two plates at ~1/8th the price
Samples are run in triplicate
Variation among replicate increases in miRNAs with low expression
There is difficulty in analyzing the data where all replicates have a different CT value

10. Validation Results

11. Sources of Down-Regulated miRNAs
Many of theses miRNAs are down regulated in cancer patients’ serum (miR-23a, 342-3p, 33a) what is their source?
Often it’s assumed cancer related miRNAs are released from the tumor
Immune system is known to be a large contributor to miRNA excretion

12. Conclusions
We have identified candidates for a validation test of serum miRNA biomarkers for Oral Cancer
Ongoing work must be preformed to determine what role overtraining plays in data analysis
Model
Training AUC
Validation AUC
23a, 205, 33a 342-3p
.91
.77
23a, 205, 33a
.90
.62
23a, 205
.83
.66
23a, 346
.85 NA

13. Acknowledgements
Supervisor Dr. Cathie Garnis Committee Members Dr. Calum Macaulay Dr. Catherine Poh Garnis Lab Members Sara MacLellan Rebecca Towle Danielle Truong James Lawson