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BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1alpha, other hypoxia-regulated pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was associated significantly with high hypoxia-inducible factor 1alpha (P = 0.003), carbonic anhydrase 9 (P = 0.04), and was inversely associated with bcl-2 expression (P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo.

Original publication




Journal article


Clin Cancer Res

Publication Date





5566 - 5571


Adenocarcinoma, Apoptosis, Carcinoma, Non-Small-Cell Lung, Cell Hypoxia, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, Lung Neoplasms, Membrane Proteins, Neoplasm Staging, Neovascularization, Pathologic, Prognosis, Proto-Oncogene Proteins, RNA, Messenger, Transcription Factors