Oncotarget

Clinical Research Papers:

Longitudinal study on circulating miRNAs in patients after lung cancer resection

Petra Leidinger _, Valentina Galata, Christina Backes, Cord Stähler, Stefanie Rheinheimer, Hanno Huwer, Eckart Meese and Andreas Keller

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Oncotarget. 2015; 6:16674-16685. https://doi.org/10.18632/oncotarget.4322

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Abstract

Petra Leidinger1, Valentina Galata2, Christina Backes2, Cord Stähler3, Stefanie Rheinheimer1, Hanno Huwer4, Eckart Meese1,* and Andreas Keller2,*

1 Department of Human Genetics, Saarland University, Homburg, Germany

2 Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany

3 Siemens AG, Strategy Division, Erlangen, Germany

4 Department of Cardiothoracic Surgery, Heart Center, Völklingen, Germany

* These authors equally contributed as senior author

Correspondence to:

Petra Leidinger, email:

Keywords: microRNA, plasma, lung cancer, metastases, follow-up

Received: January 05, 2015 Accepted: May 25, 2015 Published: May 29, 2015

Abstract

There is an urgent need of comprehensive longitudinal analyses of circulating miRNA patterns to identify dynamic changes of miRNAs in cancer patients after surgery. Here we provide longitudinal analysis of 1,205 miRNAs in plasma samples of 26 patients after lung cancer resection at 8 time points over a period of 18 months and compare them to 12 control patients. First, we report longitudinal changes with respect to the number of detected miRNAs over time and identified a significantly increased number of miRNAs in patients developing metastases (p = 0.0096). A quantitative analysis with respect to the expression level of the detected miRNAs revealed more significant changes in the miRNA levels in samples from patients without metastases compared to the non-cancer control patients. This analysis provided further evidence of miRNA plasma levels that are changing over time after tumor resection and correlate to patient outcome. Especially hsa-miR-197 could be validated by qRT-PCR as prognostic marker. Also for this miRNA, patients developing metastases had levels close to that of controls while patients that did not develop metastases showed a significant up-regulation.

In conclusion, our data indicate that the overall miRNome of a patient that later develops metastases is less affected by surgery than the miRNome of a patient who does not show metastases. The relationship between altered plasma levels of specific miRNAs with the development of metastases would partially have gone undetected by an analysis at a single time point only.


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