Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with poor prognosis of patients with resected non-small cell lung cancer
Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with poor prognosis of patients with resected non-small cell lung cancer
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Rho 鸟嘌呤核苷酸交换因子 5 和 Src 的共表达与已切除的非小细胞肺癌患者的不良预后相关。
DOI：
10.3892/or.2013.2797
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发表时间：
2013-12-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Kang
中科院分区：
文献类型：
--
作者：
He, Ping;Wu, Wei;Yang, Kang
目前缺乏特异性和敏感性足够高的分子生物标志物来准确预测非小细胞肺癌（NSCLC）患者的生存期。ARHGEF 5和Src在肿瘤发生中起重要作用。然而，ARHGEF 5和Src在NSCLC中的参与仍然未知。因此，我们评估了ARHGEF 5和Src在切除的NSCLC组织中的表达以及ARHGEF 5和Src的共表达与切除的NSCLC患者的预后的相关性。193例患者中133例（68.91%）ARHGEF 5阳性表达。本研究共入组193例NSCLC患者（男性：145例;女性：48例;平均年龄：61.84岁;年龄范围：31-84岁），其中99例为鳞状细胞癌（SCC）（51.30%），94例为腺癌（ADC）（48.70%）。ARHGEF 5主要表达于癌细胞胞浆，而癌旁肺组织未见表达。ARHGEF 5表达水平与年龄、分化程度、肿瘤分期有关。ARHGEF 5蛋白表达与Src蛋白表达在NSCLC和ADC中相关（χ 2 = 11.874，P <0.01），而在SCC中无相关性。免疫共沉淀结果显示，肺癌细胞中Src和ARHGEF 5之间存在物理相互作用。ARHGEF 5（+）/Src（+）患者的生存期较短（29.37个月比39.90个月，P = 0.029）。总之，ARHGEF 5/Src可以被认为是一个预后的生物标志物和切除NSCLC患者的治疗靶点。
Specific and sensitive enough molecular biomarkers are lacking to accurately predict the survival of non-small cell lung cancer (NSCLC) patients. ARHGEF5 and Src have been shown to play an important role in tumorigenesis. However, the involvement of ARHGEF5 and Src in NSCLC remains unknown. Therefore, we evaluated the expression of ARHGEF5 and Src in resected NSCLC tissues and the correlation of co-expression of ARHGEF5 and Src and the prognosis of patients with resected NSCLC. Positive expression of ARHGEF5 was detected in 133 cases of 193 patients (68.91%). A total of 193 NSCLC patients (male: 145; female: 48; average age: 61.84 years; age range: 31-84) were enrolled in this study, of which 99 cases were squamous cell carcinomas (SCCs) (51.30%) and 94 cases were adenocarcinomas (ADCs) (48.70%). The expression of ARHGEF5 was mainly located in the cytoplasm of tumor cells, but not in the corresponding adjacent lung tissues. The levels of ARHGEF5 were significantly associated with age, differentiation and tumor stage. ARHGEF5 protein expression was associated with Src protein expression in NSCLC (χ(2) = 11.874, P<0.01) and in ADC (χ(2) = 12.194, P<0.01), but not in SCC. Co-immunoprecipitation revealed that there was a physical interaction between Src and ARHGEF5 in lung cancer cells. The patients with ARHGEF5(+)/Src(+) had a shorter survival time compared with the other patients (29.37 months versus 39.90 months, P = 0.029). In conclusion, ARHGEF5/Src can be considered as a prognostic biomarker and a therapeutic target for patients with resected NSCLC.