Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer

Junya Fukuoka, Takeshi Fujii, Joanna H. Shih, Tatiana Dracheva, Daoud Meerzaman, Audrey Player, Kyeong Hong, Sharon Settnek, Ajay Gupta, Kenneth Buetow, Stephen Hewitt, William D. Travis, Jin Jen

Research output: Contribution to journalArticle

Abstract

We immunohistochemically examined 12 core proteins involved in the chromatin remodeling machinery using a tissue microarray composed of 150 lung adenocarcinoma (AD) and 150 squamous cell carcinoma (SCC) cases. Most of the proteins showed nuclear staining, whereas some also showed cytoplasmic or membranous staining. When the expression patterns of all tested antigens were considered, proteins with nuclear staining clustered into two major groups. Nuclear signals of BRM, Ini-1, retinoblastoma, mSin3A, HDAC1, and HAT1 clustered together, whereas nuclear signals of BRG1, BAF155, HDAC2, BAF170, and RbAP48 formed a second cluster. Additionally, two thirds of the cases on the lung tissue array had follow-up information, and survival analysis was performed for each of the tested proteins. Positive nuclear BRM (N-BRM) staining correlated with a favorable prognosis in SCC and AD patients with a 5 year-survival of 53.5% compared with 32.3% for those whose tumors were negative for N-BRM (P = 0.015). Furthermore, patients whose tumors stained positive for both N-BRM and nuclear BRG1 had a 5 year-survival of 72% compared with 33.6% (P = 0.013) for those whose tumors were positive for either or negative for both markers. In contrast, membranous BRM (M-BRM) staining correlated with a poorer prognosis in AD patients with a 5 year-survival of 16.7% compared with those without MBRM staining (38.1%; P = 0.016). These results support the notion that BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary and that the nuclear presence of BRM, its coexpression with nuclear BRG1, and the altered cellular localization of BRM (M-BRM) are useful markers for nonsmall cell lung cancer prognosis.

Original languageEnglish (US)
Pages (from-to)4314-4324
Number of pages11
JournalClinical Cancer Research
Volume10
Issue number13
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Fukuoka, J., Fujii, T., Shih, J. H., Dracheva, T., Meerzaman, D., Player, A., Hong, K., Settnek, S., Gupta, A., Buetow, K., Hewitt, S., Travis, W. D., & Jen, J. (2004). Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer. Clinical Cancer Research, 10(13), 4314-4324. https://doi.org/10.1158/1078-0432.CCR-03-0489