Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy.
Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy.
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DOI：
10.1038/sj.bjc.6604361
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发表时间：
2008-05-20
影响因子：
8.8
通讯作者：
Fujiwara Y
中科院分区：
文献类型：
--
作者：
Yoshikawa R;Nakano Y;Tao L;Koishi K;Matsumoto T;Sasako M;Tsujimura T;Hashimoto-Tamaoki T;Fujiwara Y
锌指蛋白神经胶质瘤相关癌基因同源物 1 (Gli-1) 是 Hedgehog (Hh) 信号通路的关键组成部分，该通路对于形态发生和干细胞更新至关重要，并且在许多癌症类型中失调。由于没有关于 Gli-1 表达在食管癌进展中的作用的数据，我们分析了它是否可以用于预测接受新辅助放化疗 (CRT) 的食管癌患者的疾病进展和预后。在 69 例经组织学证实的食管鳞状细胞癌 (ESCC) 患者中，25 例在术前 CRT 后表现出病理完全缓解。总生存期 (OS) 与淋巴结转移、远处转移和 CRT 显着相关，并进一步与 Gli-1 核表达和残留肿瘤的缺失相关。所有Gli-1核表达的患者（10.1%）均出现远处或淋巴结转移，七分之六的患者在13个月内死亡。此外，Gli-1核阳性癌症患者的预后显着较差（无病生存：平均 DFS 时间 250 个月 vs 1738 个月，2 年 DFS 0 vs 54.9%，P=0.009；OS：平均 OS 时间 386 vs 1742 个月，2 年 OS 16.7 vs 54.9%，P=0.001）。我们的研究提供了第一个证据，证明 Gli-1 核表达是 CRT 后 ESCC 早期复发和不良预后的强有力且独立的预测因子。这些发现表明 Hh 信号激活可能促进 CRT 后癌症的再生和进展。
The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P=0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P=0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT.
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影响因子：
4.3
作者：
Yoshikawa, Reigetsu;Fujiwara, Yoshinori;Tsujimura, Tohru
通讯作者：
Tsujimura, Tohru
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
45.3
作者：
Coia, LR;Minsky, BD;Hanks, GE
通讯作者：
Hanks, GE
影响因子：
64.8
作者：
Singh, SK;Hawkins, C;Dirks, PB
通讯作者：
Dirks, PB
影响因子：
11.2
作者：
Feldmann, Georg;Dhara, Surajit;Maitra, Anirban
通讯作者：
Maitra, Anirban