Abstract

7594 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable clinical factors to select high risk pts for adjuvant chemotherapy. miRNAs profiling is expected to indicate pts with aggressive disease and to provide prognostic information. Confounding effect of NSCLC pathology heterogeneity justifies searching for prognostic miRNAs separately in SqCLC and adenocarcinoma. Methods: Fresh frozen tumor tissue was obtained from 30 SqCLC stage I-II pts during curative pulmonary resection. Of those, 15 pts developed distant metastases and 15 had no relapse after a median follow-up of 5.4 years (range, 3.1–6.9 years). RNA was isolated from tumor sections containing ≥60% of tumor cells per section. Expression of 380 miRNAs was analyzed by RT-PCR arrays (TLDAs-Appliedbiosystems). Raw data were normalized vs. the expression of U6 RNA and calibrated by ΔΔCt method. Results: Expression of 300 miRNAs was detected in tumor tissues. Expression of three miRNAs (193a[5p], 146b[5p] and 10b) differed between groups with and without metastases (t-Student test, p<0.05). Due to the limited number of samples, proportional hazard regression for survival (Cox analysis) could not be performed on the full data set of 300 variables. Cox analysis performed for the top 5 miRNA identified with t-Student test showed significant correlation for 10b (p<0.02). The internal consistency of data sets was tested using PCA, and three samples were excluded. In this modified test set, the top 10 miRNAs (ranked according to p-value of t test) revealed two significantly correlated miRNAs in Cox analysis: 484 and 146b (5p). Similar results were obtained for miRNAs expression defined as continuous or categorized variables. Conclusions: Four miRNAs: 10b, 146b, 193a(5p) and 484 are potentially related to high metastatic propensity of early stage SqCLC. Further validation is necessary to confirm their prognostic relevance in this tumor. No significant financial relationships to disclose.

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