Conclusion
NF-κB 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-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.
Purpose
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 κ-light chain-enhancer of activated B cells (NF-κB) 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-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancer patients.
Results
Several NF-κB 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-κB is activated by RT in human rectal tumors. The baseline NF-κB 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).