title: Longitudinal study on circulating miRNAs in patients after lung cancer resection.
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.
authors.affiliation: Department of Human Genetics, Saarland University, Homburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Galata
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.affiliation: Siemens AG, Strategy Division, Erlangen, Germany.
authors.forename: Cord
authors.initials: C
authors.lastname: Stähler
authors.affiliation: Department of Human Genetics, Saarland University, Homburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rheinheimer
authors.affiliation: Department of Cardiothoracic Surgery, Heart Center, Völklingen, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Huwer
authors.affiliation: Department of Human Genetics, Saarland University, Homburg, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.affiliation: Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: follow-up; lung cancer; metastases; microRNA; plasma