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首页> 外文期刊>British Journal of Cancer >TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients
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TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

机译：TAK1调节的BIRC3表达预测食管腺癌患者对术前放化疗的耐药性

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Background: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. Methods: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. Results: In vitro , (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly ( P <0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). Conclusions: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.
机译：背景：约20％的可切除食管癌对术前放化疗具有抵抗力。在这里我们假设转化生长因子β激活激酶1（TAK1）诱导的抗凋亡基因杆状病毒凋亡抑制蛋白（BIRC）3的表达可能是对食管癌化学放疗的促凋亡作用的抵抗力。方法：使用（5Z）-7-oxozeaenolol抑制FLO-1和KYAE-1食管腺癌细胞中TAK1激酶的活性。通过qRT-PCR在接受术前多西紫杉醇，顺铂，5-氟尿嘧啶和同时放疗的65例预处理冷冻活检中测量了BIRC3 mRNA的表达。进行接收者操作员特征（ROC）分析，以确定BIRC3表达水平在区分敏感或耐药癌症患者中的表现。结果：在体外，（5Z）-7-氧杂烯醇显着降低了FLO-1和KYAE-1细胞中BIRC3的表达。暴露于化学治疗剂或放疗加（5Z）-7-氧杂烯醇会产生强烈的协同抗凋亡作用。在患者中，BIRC3的中位表达在腺癌中显着高于（P ＜0.0001）在更敏感的鳞状细胞癌亚型中。 BIRC3表达显着地区分了敏感性或耐药性腺癌患者（AUC-ROC = 0.7773和0.8074，分别基于基于大小的病理反应或Mandard肿瘤消退等级分类）。结论：BIRC3表达可能是预测食道腺癌患者的有效生物标志物，这些患者最有可能受益于术前放化疗。

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