Higher expression of MIR-133b is associated with better efficacy of erlotinib as the second or third line in non-small cell lung cancer patients

Alessandra Bisagni, Maria Pagano, Sally Maramotti, Francesca Zanelli, Martina Bonacini, Elena Tagliavini, Luca Braglia, Massimiliano Paci, Andrea Mozzarelli, Stefania Croci

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib, erlotinib and afatinib) are indicated as first-line therapy in patients with non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations in the EGFR gene. Erlotinib is also used in second and third-line therapy for patients whose tumors have wild type EGFR but to date there are no validated biomarkers useful to identify which patients may benefit from this treatment. The expression level of four miRNAs: miR-133b, -146a, -7 and -21 which target EGFR was investigated by real-time PCR in tumor specimens from NSCLC patients treated with erlotinib administered as the second or third line. We found that miR-133b expression level better discriminated responder from non-responder patients to erlotinib. Higher levels of miR-133b in NSCLCs were associated with longer progression-free survival time of patients. Functional analyses on miR-133b through transfection of a miR-133b mimic in A549 and H1299 NSCLC cell lines indicated that increasing miR-133b expression level led to a decreased cell growth and altered morphology but did not affect sensitivity to erlotinib. The detection of miR-133b expression levels in tumors help in the identification of NSCLC patients with a better prognosis and who are likely to benefit from second and third-line therapy with erlotinib.

Original languageEnglish
Article numbere0196350
JournalPLoS One
Volume13
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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lung neoplasms
Non-Small Cell Lung Carcinoma
Cells
Epidermal Growth Factor Receptor
Tumors
cells
neoplasms
therapeutics
Neoplasms
erbB-1 Genes
Cell growth
Biomarkers
Ports and harbors
MicroRNAs
Protein-Tyrosine Kinases
transfection
Therapeutics
Erlotinib Hydrochloride
prognosis
Disease-Free Survival

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Higher expression of MIR-133b is associated with better efficacy of erlotinib as the second or third line in non-small cell lung cancer patients. / Bisagni, Alessandra; Pagano, Maria; Maramotti, Sally; Zanelli, Francesca; Bonacini, Martina; Tagliavini, Elena; Braglia, Luca; Paci, Massimiliano; Mozzarelli, Andrea; Croci, Stefania.

In: PLoS One, Vol. 13, No. 4, e0196350, 01.04.2018.

Research output: Contribution to journalArticle

Bisagni, Alessandra ; Pagano, Maria ; Maramotti, Sally ; Zanelli, Francesca ; Bonacini, Martina ; Tagliavini, Elena ; Braglia, Luca ; Paci, Massimiliano ; Mozzarelli, Andrea ; Croci, Stefania. / Higher expression of MIR-133b is associated with better efficacy of erlotinib as the second or third line in non-small cell lung cancer patients. In: PLoS One. 2018 ; Vol. 13, No. 4.
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