Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05).

Jörger Messerli, Marianne; Baty, F; Früh, M; Stahel, R A; Betticher, D C; von Moos, Rodica; Ochsenbein, Adrian; Pless, M; Gautschi, O; Rothschild, S; Brauchli, P; Klingbiel, Dirk; Zappa, F; Brutsche, M (2014). Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05). Lung cancer, 85(2), pp. 306-313. Elsevier 10.1016/j.lungcan.2014.04.014

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OBJECTIVES Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. MATERIALS AND METHODS Fifty patients with baseline and 24 h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). RESULTS Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR=6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). CONCLUSION Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Medical Education > Institute of Complementary and Integrative Medicine (IKIM)
08 Faculty of Science > Department of Mathematics and Statistics > Institute of Mathematical Statistics and Actuarial Science
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Jörger Messerli, Marianne; von Moos, Rodica; Ochsenbein, Adrian and Klingbiel, Dirk

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
300 Social sciences, sociology & anthropology > 360 Social problems & social services
500 Science > 510 Mathematics
600 Technology > 610 Medicine & health

ISSN:

0169-5002

Publisher:

Elsevier

Language:

English

Submitter:

Monique Ryter

Date Deposited:

09 Feb 2015 08:08

Last Modified:

27 Aug 2015 10:47

Publisher DOI:

10.1016/j.lungcan.2014.04.014

PubMed ID:

24928469

Uncontrolled Keywords:

Bevacizumab, Biomarkers, Chemotherapy, Erlotinib, Lung cancer, MicroRNA's

BORIS DOI:

10.7892/boris.62845

URI:

https://boris.unibe.ch/id/eprint/62845

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