Zhao Shilei, Guo Wei, Li Jinxiu, Yu Wendan, Guo Tao, Deng Wuguo, Gu Chundong
The First Affiliated Hospital, Institute of Cancer Stem Cell, Lung Cancer Diagnosis and Treatment Center, Dalian Medical University, Dalian, People's Republic of China.
Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China; State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, People's Republic of China.
Onco Targets Ther. 2016 May 5;9:2683-92. doi: 10.2147/OTT.S99939. eCollection 2016.
Prognosis of small (≤2 cm) invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma) that are independent of TNM (tumor, nodes, metastases) staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma.
A total of 75 patients with small invasive lung adenocarcinoma after complete resection were enrolled from January 2008 to December 2010. Immunohistochemical staining was used to detect the expression of YBX1, and receiver operating characteristic curve analysis was performed to precisely assess the overall expression of YBX1. Meanwhile, primary lesions were identified based on the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society's classification of lung adenocarcinoma. The effect of different clinicopathological factors on patients' survival was examined. Furthermore, Western blot analysis was used to show the expression of YBX1 in vitro.
Sensitivity and specificity of YBX1 for detecting small invasive lung adenocarcinoma from normal surrounding tissue were 66.7% and 74.7% (area under the receiver operating characteristic curve =0.731; P<0.001), respectively. High YBX1 expression was detected in 31 (41.3%) patients, and in A549, H322, Hcc827, and H1299 lung adenocarcinoma cells but not in HLF cells. In addition to sex, age, tumor size, TNM staging, pleural invasion, and lymph node metastasis, the expression of YBX1 was associated with the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society pathological grade risk (P=0.026) and differentiation (P=0.009). The patients with low YBX1 expression lived longer than those with high expression (5-year overall survival: 52.3% vs 79.0%; P=0.039) and showed fewer recurrences (P=0.024). In multivariate analyses, high YBX1 expression (odds ratio =2.737; 95% confidence interval: 1.058-7.082; P=0.038) was shown as an independent risk factor of overall survival but not of disease-free survival (odds ratio =1.696; 95% confidence interval: 0.616-4.673; P=0.307).
YBX1 is an important predictor for the prognosis in patients with small invasive lung adenocarcinoma after complete resection.
小（≤2 cm）浸润性肺腺癌的预后仍然较差，在肺腺癌完全手术切除后的患者中识别高危个体已成为一个紧迫的问题。据报道，YBX1能够在许多癌症（除肺腺癌外）中预测预后，且独立于TNM（肿瘤、淋巴结、转移）分期，尤其是小浸润性肺腺癌。因此，我们研究了YBX1表达对小浸润性肺腺癌患者预后和复发的意义。
2008年1月至2010年12月共纳入75例小浸润性肺腺癌完全切除术后的患者。采用免疫组织化学染色检测YBX1的表达，并进行受试者工作特征曲线分析以精确评估YBX1的整体表达。同时，根据国际肺癌研究协会、美国胸科学会和欧洲呼吸学会的肺腺癌分类确定原发性病变。研究了不同临床病理因素对患者生存的影响。此外，采用蛋白质免疫印迹分析在体外显示YBX1的表达。
YBX1用于从正常周围组织中检测小浸润性肺腺癌的敏感性和特异性分别为66.7%和74.7%（受试者工作特征曲线下面积=0.731；P<0.001）。在31例（41.3%）患者中检测到YBX1高表达，在A549、H322、Hcc827和H1299肺腺癌细胞中也检测到YBX1高表达，但在HLF细胞中未检测到。除性别、年龄、肿瘤大小、TNM分期、胸膜侵犯和淋巴结转移外，YBX1的表达与国际肺癌研究协会、美国胸科学会和欧洲呼吸学会的病理分级风险（P=0.026）和分化程度（P=0.009）相关。YBX1低表达的患者比高表达的患者生存时间更长（5年总生存率：52.3%对79.0%；P=0.039），且复发较少（P=0.024）。在多因素分析中，YBX1高表达（比值比=2.737；95%置信区间：1.058 - 7.082；P=0.038）被显示为总生存的独立危险因素，但不是无病生存的独立危险因素（比值比=1.696；95%置信区间：0.616 - 4.673；P=0.307）。
YBX1是小浸润性肺腺癌完全切除术后患者预后的重要预测指标。
