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The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR- and KRAS-mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT-qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR-mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR-mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course., (© 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)

Recent studies have demonstrated the possibility to detect genetic changes in plasma DNA of cancer patients. The goal of this study was to validate a panel of molecular markers for lung cancer detection in plasma DNA. Three markers, p53, FHIT and microsatellite alterations at loci on chromosome 3, were used to detect mutations in tumor and plasma DNA of 64 stage I-III non small cell lung cancer patients. p53 mutations were studied by direct sequencing of exons 5 through 8 in tumor DNA and by plaque hybridization assay and sequencing in plasma DNA. Allelic losses were evaluated by fluorescent PCR in tumor and plasma DNA. p53 genomic mutations were detected in 26 (40.6%) of 64 tumor DNA samples and the identical mutation was identified in plasma of 19 (73.1%) of them. Microsatellite alterations at FHIT and 3p loci were observed in 40 (62.5%) tumors and in 23 (35.9%) plasma samples. Of the 40 patients showing microsatellite alterations in tumors, 19 (47.5%) displayed the same change in plasma DNA. At least 1 of the 3 genetic markers (p53, FHIT and 3p) was altered in plasma of 51.6% of all patients and 60.7% of stage I patients. Moreover, genetic markers in plasma identified 29 of 45 (64.4%) of all stages and 15 of 22 (68.2%) of stage I patients whose tumors had an alteration. These results provide the proof of principle that plasma DNA alterations are tumor-specific in most cases and support blood testing as a noninvasive strategy for early detection., (Copyright 2003 Wiley-Liss, Inc.)