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National Institute of Environmental Health Sciences

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Publication Detail

Title: Nuclear factor ýý-light chain-enhancer of activated B cells is activated by radiotherapy and is prognostic for overall survival in patients with rectal cancer treated with preoperative fluorouracil-based chemoradiotheraphy.

Authors: O'Neil, Bert H; Funkhouser, William K; Calvo, Benjamin F; Meyers, Michael O; Kim, Hong Jin; Goldberg, Richard M; Bernard, Stephen A; Caskey, Laura; Deal, Allison M; Wright, Fred; Baldwin, Albert S; Tepper, Joel E

Published In Int J Radiat Oncol Biol Phys, (2011 Jul 1)

Abstract: Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor ýý-light chain-enhancer of activated B cells (NF-ýýB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-ýýB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-ýýB activity correlates with the outcome in rectal cancer patients.A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-ýýB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-ýýB-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-ýýB subunit nuclear localization using immunohistochemistry.Several NF-ýýB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-ýýB is activated by RT in human rectal tumors. The baseline NF-ýýB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040).NF-ýýB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-ýýB target gene upregulation on the response to RT. Our results suggest that NF-ýýB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.

PubMed ID: 20630669 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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