Molecular Biology Reports

, Volume 46, Issue 4, pp 4001–4008 | Cite as

The expression level of fibulin-2 in the circulating RNA (ctRNA) of epithelial tumor cells of peripheral blood and tumor tissue of patients with metastatic lung cancer

  • Mukaddes Avsar
  • Makbule Tambas
  • Zubeyde Yalniz
  • Demet Akdeniz
  • Seref Bugra Tuncer
  • Seda Kilic
  • Ozge Sukruoglu Erdogan
  • Rumeysa Ciftci
  • Nergiz Dagoglu
  • Sezai Vatansever
  • Hulya YaziciEmail author
Original Article


The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124) = 14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p = 0.997), bone versus brain metastases (p = 0994), bone metastases versus two primary tumors (p = 0.999), brain metastases versus two primary tumors (p = 0.999), brain metastases versus non-metastatic (p = 0.755), non-metastatic versus two primary tumors (p = 0.996), non-metastatic versus all other metastatic patients (p = 0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells of peripheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.


Fibulin-2 (FBLN2) Gene expression ctRNA Lung cancer Metastasis 



All authors thank the participants and the Research Fund of Istanbul University for funding (Project No. 24255) to study.


The present work was supported by the Research Fund of Istanbul University. Project No. 24255.

Compliance with ethical standards

Ethical approval

All human participant involving procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval was granted by the Local and Clinical Research Ethics Committee of Istanbul Medical Faculty, and all participants (patients and controls) provided written informed consent in accordance with the Declaration of Helsinki (Protocol Number: 333-962).

Informed consent

The informed consents were obtained from all participants that were included in the study. The study was approved by the Ethics Committee of Istanbul Medical Faculty in Istanbul University (Ethical Approval No: 2012/333-962).

Research involving human and animal participants

This article contains no studies conducted with animals.

Conflict of interest

The authors declare that they have no conflict of interests.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mukaddes Avsar
    • 1
  • Makbule Tambas
    • 2
  • Zubeyde Yalniz
    • 1
  • Demet Akdeniz
    • 1
  • Seref Bugra Tuncer
    • 1
  • Seda Kilic
    • 1
  • Ozge Sukruoglu Erdogan
    • 1
  • Rumeysa Ciftci
    • 3
  • Nergiz Dagoglu
    • 2
  • Sezai Vatansever
    • 3
  • Hulya Yazici
    • 1
    Email author
  1. 1.Department of Cancer Genetics, Institute of OncologyIstanbul UniversityIstanbulTurkey
  2. 2.Department of Radiation Oncology, Institute of OncologyIstanbul UniversityIstanbulTurkey
  3. 3.Department of Medical Oncology, Institute of OncologyIstanbul UniversityIstanbulTurkey

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