Brain metastasis (BM) can affect ~25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. microRNAs (miRNAs) regulate the expression of target mRNAs. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment, and prognosis. We investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from seven patients with BM (BM+) and six without BM (BM−). Using t-test and further qRT-PCR validation, eight miRNAs were confirmed to be significantly differentially-expressed. Of these, expression of miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM− patients. This classifier was used on a validation cohort (n=15) and it correctly classified 12/15 patients. Gene expression analysis comparing A549 parental and A549 cells stably transfected to over-express miR-328 (A549–328) identified several significantly differentially-expressed genes. PRKCA was one of the genes over-expressed in A549–328 cells. Additionally, A549–328 cells had significantly increased cell migration compared to A549 cells, which was significantly reduced upon PRKCA knockdown. In summary, miR-328 has a role in conferring migratory potential to NSCLC cells working in part through PRKCA and with further corroboration in additional independent cohorts, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients at higher risk for developing BM.

Higher tumor miR-92a-2* levels are associated with chemoresistance and with decreased survival in patients with SCLC. Tumor miR-92a-2* may have application in screening patients with SCLC at risk for de novo chemoresistance in an effort to design more tailored clinical trials for this subpopulation. Further validation in independent sample sets is warranted.

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Direct intraoperative cholangiography, endoscopic retrograde cholangiopancreatography, T-tube cholangiography, and percutaneous transhepatic cholangiography are routine procedures performed by interventionalists. Radiologists must understand how to interpret direct cholangiography to facilitate multidisciplinary communication, correlate findings with magnetic resonance cholangiopancreatography, and improve patient care.

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