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Circulating microRNA Expression Profiles in Early Stage Non-Small Cell Lung Cancer

Heegaard, N.H.H., Schetter, A.J., Welsch, J.A., Yoneda, M., Bowman, E.D., Harris, C.C.

Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure microRNA levels in serum and plasma. Here we study paired serum and plasma samples from 220 patients with early stage NSCLC and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples and microRNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expression of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared to controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC.

Citation

Heegaard, N.H.H., Schetter, A.J., Welsch, J.A., Yoneda, M., Bowman, E.D., Harris, C.C. "Circulating microRNA Expression Profiles in Early Stage Non-Small Cell Lung Cancer" International Journal of Cancer (2012): 1,378–86