Prognostic impact of a 3-MicroRNA signature in cytological samples of small cell lung cancer

Abstract

Background: Small cell lung cancer (SCLC) is a highly aggressive neoplasm that accounts for approximately 10% to 15% of lung cancers. In most cases, the diagnosis relies on cytology and needs to be confirmed by immunohistochemistry. Although several genetic and molecular abnormalities have been recorded, molecular markers able to predict the prognosis are still lacking. MicroRNA (miRNA) signatures have been recently proposed as useful biomarkers in lung cancer because of their high stability during standard sample processing.

Methods: Cytological samples for 50 patients with SCLC were collected from primary tumors (n = 25) and metastases (n = 25) by means of fine-needle aspiration (FNA) or bronchial washing (BW); they were fixed in ethanol (FNA) or Duboscq-Brazil fluid (BW). The 3-miRNA panel expression (miR-192, miR-200c, and miR-205) was quantified with a TaqMan polymerase chain reaction miRNA assay and was compared with overall survival (OS) and clinicopathological data.

Results: All samples had sufficient RNA for the miRNA expression analysis to be performed, regardless of the sample source or the fixative medium. Patients with a low expression level of the 3-miRNA panel were associated with better OS in univariate (P = .032) and multivariate analyses (P = .022). Moreover, in the group of patients older than the mean age of our cohort (65.8 years), a significant OS advantage (P = .013) was seen for patients with a low expression level of the 3-miRNA panel.

Conclusions: A specific 3-miRNA signature is potentially useful for predicting survival for patients with SCLC, and it may be feasible with cytological samples taken during standard diagnostic procedures. Cancer Cytopathol 2016;124:621-9. © 2016 American Cancer Society.

Keywords: biomarkers; bronchial brushings; fine-needle cytology; microRNA 192 (miR-192); microRNA 200c (miR-200c); microRNA 205 (miR-205); prognosis; small cell lung carcinoma.