Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma
Pretherapy nuclear factor-κB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma
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DOI：
10.1158/1535-7163.mct-06-0351
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发表时间：
2006-11-01
影响因子：
5.7
通讯作者：
Ajani, Jaffer A.
中科院分区：
文献类型：
--
作者：
Izzo, Julie G.;Correa, Arlene M.;Ajani, Jaffer A.
背景：转录因子核因子- κ B （nf - κ B）似乎与食管癌的侵袭性临床生物学（放化疗耐药和转移进展）有关。我们假设活化的NF-kappa B将定义临床生物学，而不管化疗类型或给药顺序如何。方法：对治疗前和/或治疗后的癌症标本进行活化nf - κ B检查，并与放化疗的病理反应、转移潜力、总生存期、无病生存期、化疗类型或使用顺序相关。结果：对80例接受化疗和放疗的患者进行了研究。在任何治疗前激活nf - κ B与缺乏完全病理反应相关（pathCR, P = 0.006）。达到< pathCR的58例患者中有45例（78%）在治疗前和/或治疗后癌症标本中激活nf - κ B，而达到pathCR的22例患者中有2例（9%）激活nf - κ B （P = 0.001）。47例NF-kappa B活化的癌症患者中有24例（51%）发生转移，而22例NF-kappa B阴性的癌症患者中有7例（21%）发生转移（P = 0.01）。在中位随访32个月时，47例活化NF-kappa B癌患者中有25例（53%）死亡，而33例NF-kappa B阴性癌患者中有3例（9%）死亡。在多变量模型中，NF-kappa B激活是无病生存（P = 0.01）和总生存（P = 0.007）的唯一独立预测因子。化疗类别或其顺序对nf - κ B表达或患者预后没有影响。结论：我们的数据首次显示预处理激活的NF-kappa B与食管癌的临床生物学显著相关，最重要的是与pathCR相关。为了治疗性地利用nf - κ b调节基因及其通路，需要进一步的研究。
Background: Transcriptional factor nuclear factor-kappa B (NF-kappa B) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-kappa B would define clinical biology irrespective of the type of chemotherapy or sequence administered. Methods: Pretherapy and/or posttherapy cancer specimens were examined for activated NF-kappa B and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used. Findings: Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-kappa B prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving < pathCR had activated NF-kappa B in pretherapy and/or posttherapy cancer specimens versus 2 (9%) of 22 patients with pathCR (P = 0.001). Twenty-four (51%) of 47 patients with activated NF-kappa B in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-kappa B in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-kappa B cancer had died versus 3 (9%) of 33 patients with negative NF-kappa B cancer. NF-kappa B activation was the only independent predictor of disease-free survival (P = 0.01) and overall survival (P = 0.007) in a multivariate model. The class of chemotherapy or its sequence had no effect on NF-kappa B expression or patient outcome. Conclusions: Our data are the first to show that pretreatment-activated NF-kappa B significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-kappa B-regulated genes and their pathways, further research is warranted.