Expression of TGFβ-1 and EHD1 correlated with survival of non-small cell Lung cancer
Expression of TGFβ-1 and EHD1 correlated with survival of non-small cell Lung cancer
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DOI：
10.1007/s13277-014-2164-x
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发表时间：
2014-09-01
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影响因子：
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通讯作者：
Dong, Xiaoqun
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文献类型：
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作者：
Gao, Yuanyuan;Wang, Yan;Dong, Xiaoqun
转化生长因子-β 1（TGF β-1）信号传导受内吞途径调节。为了阐明TGF β 1的预后价值并验证内吞作用在耐药中的作用，我们检测了TGF β 1和Eps 15同源结构域1（EHD 1）在非小细胞肺癌（NSCLC）中的表达及其与肿瘤特征和NSCLC患者生存率的相关性。采用免疫组织化学方法检测105例NSCLC患者石蜡切片中TGF β 1和EHD 1的表达。采用Kaplan-Meier法、log-rank检验和多因素考克斯比例风险回归模型分析总生存期（OS）。TGF β 1和EHD 1的阳性表达率分别为52.38%和39.05%。非辅助化疗组EHD 1阴性表达者的OS较EGFR阳性（P = 0.006）和辅助化疗组（P = 0.003）明显延长。同时TGF β 1阳性和EHD 1阴性（联合标志物）的NSCLC患者与更好的OS显著相关（P = 0.001）。美国癌症联合委员会（AJCC）状态和联合标志物是OS的独立预后指标（HR（95%CI）分别为1.576（1.112-2.232），P = 0.011和HR 0.349（0.180-0.673），P = 0.002）。我们确定一致的TGF β 1阳性和EHD 1阴性是NSCLC的一个强有力的有利预后因素。我们的研究结果可能有助于我们选择和优化个性化治疗策略。
Transforming growth factor-beta 1 (TGF beta-1) signaling is regulated by endocytotic pathway. To clarify the prognostic value of TGF beta-1 and to verify the involvement of endocytosis in drug resistance, we examined the expression of TGF beta-1 and Eps15 homology domain 1 (EHD1) in non-small cell lung cancer (NSCLC) and its association with tumor characteristics and survival of patients with NSCLC. Expression of TGF beta-1 and EHD1 was evaluated by immunohistochemistry in paraffin sections from 105 NSCLC patients. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazard regression model. Positive immunostaining of TGF beta-1 and EHD1 was detected in 52.38 and 39.05 % of NSCLC samples, respectively. In non-adjuvant chemotherapy-treated group (P = 0.006) and epidermal growth factor receptor (EGFR) (+) group (P = 0.038), patients with TGF beta-1 expression had a longer OS. EHD1 negative expression predicted a longer OS (P = 0.003), especially in EGFR (+) (P = 0.006) and adjuvant chemotherapy-treated patients (P = 0.003). NSCLC patients with concurrent positive TGF beta-1 and negative EHD1 (combined markers) were significantly correlated with better OS (P = 0.001). American Joint Committee on Cancer (AJCC) status and combined markers were independent prognostic indicators for OS (HR (95 % CI) 1.576 (1.112-2.232), P = 0.011 and HR 0.349 (0.180-0.673), P = 0.002, respectively). We identified concordant TGF beta-1 positive and EHD1 negative as a strong favorable prognosis factor in NSCLC. Our results may help us to select and optimize strategies for individualized therapy.