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Show HONORS COLLEGE SPRING 2013 PREDICTING RESPONSETO COMBINED BIOLOGIC THERAPY IN NON-SMALL CELL LUNG CANCER USING CIRCULATING MICRORNAS Sydney Truong (Philip Bernard) Department of Bioengineering University of Utah Patients diagnosed with non-small cell lung cancer have very limited treatment options, as this subtype of lung cancer has been found to be relatively unresponsive to chemotherapy. Biologic treatments such as EGFR and VEGFR inhibitors, however, are effective in select cases. Additionally, biologic treatments are an expensive form of treatment. Therefore, a minimally invasive method of predicting patient response to therapy is needed to minimize unnecessary cost to the patient and prescribe the best form of therapy. MicroRNA present a potential solution to this problem, as they are differentially expressed within cancerous cells in comparison to non-cancerous cells. MicroRNAs are also released by cells into the blood. W e hypothesized that circulating microRNA expression levels are dependent upon lung cancer treatment status and may be used to determine patient response to treatment at an early stage of therapy. Pre-treatment and six-week post-treatment serum samples were collected from 27 lung cancer patients receiving the combined biologic treatment Bevacizumab and Erlotinib. MicroRNA was isolated from the serum samples and quantified via qRT-PCR. Expression levels were then compared using pairwise t-test comparisons and the prognostic value of pre-treatment expression was determined using ROC/ AUC analyses. Two microRNAs (hsa-miR-501-5p and hsa-miR-1911) showed significant (p<0.05) changes in expression level between pre-treatment and post-treatment samples. Furthermore, hsa-miRs-501-5p, -1911, and -509-5p exhibited favorable prognostic values (>0.75). These results illustrate that circulating microRNA expression does indeed change depending upon treatment status in lung cancer patients. Further investigation includes determining how early this change can be detected and the biologic source of these changes. |
