EGFR regulation by microRNA in lung cancer: Correlation with clinical response and survival to gefitinib and EGFR expression in cell lines

G. J. Weiss, L. T. Bemis, E. Nakajima, M. Sugita, D. K. Birks, W. A. Robinson, M. Varella-Garcia, P. A. Bunn, J. Haney, B. A. Helfrich, H. Kato, F. R. Hirsch, W. A. Franklin

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Background: Allelic loss in chromosome 3p is one of the most frequent and earliest genetic events in lung carcinogenesis. We investigated if the loss of microRNA-128b, a microRNA located on chromosome 3p and a putative regulator of epidermal growth factor receptor (EGFR), correlated with response to targeted EGFR inhibition. Loss of microRNA-128b would be equivalent to losing a tumor suppressor gene because it would allow increased expression of EGFR. Patients and Methods: We initially showed that microRNA-128b is a regulator of EGFR in non-small-cell lung cancer (NSCLC) cell lines. We tested microRNA-128b expression levels by quantitative RT-PCR, genomic copy number by quantitative PCR, and mutations in the mature microRNA-128b by sequencing. We determined whether microRNA-128b loss of heterozygosity (LOH) in 58 NSCLC patient samples correlated with response to gefitinib and evaluated EGFR expression and mutation status. Results: We determined that microRNA-128b directly regulates EGFR. MicroRNA-128b LOH was frequent in tumor samples and correlated significantly with clinical response and survival following gefitinib. EGFR expression and mutation status did not correlate with survival outcome. Conclusion: Identifying microRNA regulators of oncogenes could have far-reaching implications for lung cancer patients including improving patient selection for targeted agents, development of novel therapeutics, or development as early biomarkers of disease.

Original languageEnglish (US)
Pages (from-to)1053-1059
Number of pages7
JournalAnnals of Oncology
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

MicroRNAs
Epidermal Growth Factor Receptor
Lung Neoplasms
Cell Line
Survival
Loss of Heterozygosity
Non-Small Cell Lung Carcinoma
Mutation
Chromosomes
gefitinib
Polymerase Chain Reaction
Tumor Suppressor Genes
Oncogenes
Patient Selection
Carcinogenesis
Biomarkers
Lung

Keywords

  • Epidermal growth factor receptor
  • Gefitinib
  • MicroRNA
  • Non-small-cell lung cancer

Cite this

EGFR regulation by microRNA in lung cancer : Correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. / Weiss, G. J.; Bemis, L. T.; Nakajima, E.; Sugita, M.; Birks, D. K.; Robinson, W. A.; Varella-Garcia, M.; Bunn, P. A.; Haney, J.; Helfrich, B. A.; Kato, H.; Hirsch, F. R.; Franklin, W. A.

In: Annals of Oncology, Vol. 19, No. 6, 01.06.2008, p. 1053-1059.

Research output: Contribution to journalArticle

Weiss, GJ, Bemis, LT, Nakajima, E, Sugita, M, Birks, DK, Robinson, WA, Varella-Garcia, M, Bunn, PA, Haney, J, Helfrich, BA, Kato, H, Hirsch, FR & Franklin, WA 2008, 'EGFR regulation by microRNA in lung cancer: Correlation with clinical response and survival to gefitinib and EGFR expression in cell lines', Annals of Oncology, vol. 19, no. 6, pp. 1053-1059. https://doi.org/10.1093/annonc/mdn006
Weiss, G. J. ; Bemis, L. T. ; Nakajima, E. ; Sugita, M. ; Birks, D. K. ; Robinson, W. A. ; Varella-Garcia, M. ; Bunn, P. A. ; Haney, J. ; Helfrich, B. A. ; Kato, H. ; Hirsch, F. R. ; Franklin, W. A. / EGFR regulation by microRNA in lung cancer : Correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. In: Annals of Oncology. 2008 ; Vol. 19, No. 6. pp. 1053-1059.
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T2 - Correlation with clinical response and survival to gefitinib and EGFR expression in cell lines

AU - Weiss, G. J.

AU - Bemis, L. T.

AU - Nakajima, E.

AU - Sugita, M.

AU - Birks, D. K.

AU - Robinson, W. A.

AU - Varella-Garcia, M.

AU - Bunn, P. A.

AU - Haney, J.

AU - Helfrich, B. A.

AU - Kato, H.

AU - Hirsch, F. R.

AU - Franklin, W. A.

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N2 - Background: Allelic loss in chromosome 3p is one of the most frequent and earliest genetic events in lung carcinogenesis. We investigated if the loss of microRNA-128b, a microRNA located on chromosome 3p and a putative regulator of epidermal growth factor receptor (EGFR), correlated with response to targeted EGFR inhibition. Loss of microRNA-128b would be equivalent to losing a tumor suppressor gene because it would allow increased expression of EGFR. Patients and Methods: We initially showed that microRNA-128b is a regulator of EGFR in non-small-cell lung cancer (NSCLC) cell lines. We tested microRNA-128b expression levels by quantitative RT-PCR, genomic copy number by quantitative PCR, and mutations in the mature microRNA-128b by sequencing. We determined whether microRNA-128b loss of heterozygosity (LOH) in 58 NSCLC patient samples correlated with response to gefitinib and evaluated EGFR expression and mutation status. Results: We determined that microRNA-128b directly regulates EGFR. MicroRNA-128b LOH was frequent in tumor samples and correlated significantly with clinical response and survival following gefitinib. EGFR expression and mutation status did not correlate with survival outcome. Conclusion: Identifying microRNA regulators of oncogenes could have far-reaching implications for lung cancer patients including improving patient selection for targeted agents, development of novel therapeutics, or development as early biomarkers of disease.

AB - Background: Allelic loss in chromosome 3p is one of the most frequent and earliest genetic events in lung carcinogenesis. We investigated if the loss of microRNA-128b, a microRNA located on chromosome 3p and a putative regulator of epidermal growth factor receptor (EGFR), correlated with response to targeted EGFR inhibition. Loss of microRNA-128b would be equivalent to losing a tumor suppressor gene because it would allow increased expression of EGFR. Patients and Methods: We initially showed that microRNA-128b is a regulator of EGFR in non-small-cell lung cancer (NSCLC) cell lines. We tested microRNA-128b expression levels by quantitative RT-PCR, genomic copy number by quantitative PCR, and mutations in the mature microRNA-128b by sequencing. We determined whether microRNA-128b loss of heterozygosity (LOH) in 58 NSCLC patient samples correlated with response to gefitinib and evaluated EGFR expression and mutation status. Results: We determined that microRNA-128b directly regulates EGFR. MicroRNA-128b LOH was frequent in tumor samples and correlated significantly with clinical response and survival following gefitinib. EGFR expression and mutation status did not correlate with survival outcome. Conclusion: Identifying microRNA regulators of oncogenes could have far-reaching implications for lung cancer patients including improving patient selection for targeted agents, development of novel therapeutics, or development as early biomarkers of disease.

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