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MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature.

ABSTRACT: Lung cancer is the most common cause of cancer deaths worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression. Many studies have reported that alterations in miRNA expression are involved in several human tumors. We have previously identified a circulating miRNA signature classifier (MSC) able to discriminate lung cancer with more aggressive features. In the present work, microarray miRNA profiling of tumor tissues collected from 19 lung cancer patients with an available MSC result were perform in order to find a possible association between miRNA expression and the MSC risk level. Eleven tissue mature miRNAs and six miRNA precursors were observed to be associated with the plasma MSC risk level of patients. Not one of these miRNAs was included in the MSC algorithm. A pathway enrichment analysis revealed a role of these miRNA in the main pathways determining lung cancer aggressiveness. Overall, these findings add to the knowledge that tissue and plasma miRNAs behave as excellent diagnostic and prognostic biomarkers, which may find rapid application in clinical settings.

SUBMITTER: Fortunato O

PROVIDER: S-EPMC5040965 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature.

Fortunato Orazio O Verri Carla C Pastorino Ugo U Sozzi Gabriella G Boeri Mattia M

Microarrays (Basel, Switzerland) 20160705 3

Lung cancer is the most common cause of cancer deaths worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression. Many studies have reported that alterations in miRNA expression are involved in several human tumors. We have previously identified a circulating miRNA signature classifier (MSC) able to discriminate lung cancer with more aggressive features. In the present work, microarray miRNA profiling of tumor tissues collected from 19 lung cancer patients with an ava ...[more]

PMID: 27600084

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Project description:BackgroundDespite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.MethodsWe profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.ResultsmiR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.ConclusionsOverall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.

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MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature.

Publications

MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature.

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