Abstract
BackgroundDicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. We aimed to find patient groups within the cohort that might have an advantage of receiving adjunctive therapies.MethodsDicer expression in the cytoplasm and Drosha expression in the nucleus were evaluated by manual immunohistochemistry of tissue microarrays (TMAs), including tumor tissue samples from 335 patients with resected stages I to IIIA NSCLC. In addition, in situ hybridizations of TMAs for visualization of miR-126 were performed. Kaplan–Meier analysis was performed, and the log-rank test via SPSS v.22 was used for estimating significance levels.ResultsIn patients with normal performance status (ECOG = 0, n = 197), high Dicer expression entailed a significantly better prognosis than low Dicer expression (P = 0.024). Dicer had no significant prognostic value in patients with reduced performance status (ECOG = 1–2, n = 138). High Drosha expression was significantly correlated with high levels of the microRNA 126 (miR-126) (P = 0.004). Drosha/miR-126 co-expression had a significant negative impact on the disease-specific survival (DSS) rate (P < 0.001). Multivariate analyses revealed that the interaction Dicer*Histology (P = 0.049) and Drosha/miR-126 co-expression (P = 0.033) were independent prognostic factors.ConclusionsIn NSCLC patients with normal performance status, Dicer is a positive prognostic factor. The importance of Drosha as a prognostic factor in our material seems to be related to miR-126 and possibly other microRNAs.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6890-14-45) contains supplementary material, which is available to authorized users.
Highlights
Dicer and Drosha are important enzymes for processing microRNAs
Patients and clinical samples The study examined primary tumor tissues from anonymized patients diagnosed with non-small cell lung cancer (NSCLC) pathologic stage I to IIIA within the period from 1990 to 2004 at the University Hospital of North Norway (UNN) and Nordland Central Hospital (NLCH)
For patients with high Drosha/high microRNA 126 (miR-126), the HR was 2.1 (1.1–4.0 at 95% CI, p < 0.001) compared to patients with high Drosha/low miR-126 (Table 1). In this large-scale study comprising primary tumors from 335 patients, we investigated the prognostic impact of the miRNA regulators Dicer and Drosha in NSCLC
Summary
Dicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. An increasing number of reports have implicated a role for miRNAs in lung cancer progression [2,3]. It is believed that miRNA expression is important in NSCLC development [5,6]. Expression profiling of miRNAs in normal and diseased lung tissues have revealed unique expression patterns, and a number of miRNAs have been characterized as tumor suppressor genes or oncogenes [7,8,9,10,11,12,13]
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