Wang Yixuan, Li Nan, Che Shuanlong, Jin Tiefeng, Piao Junjie, Liu Shuangping, Lin Zhenhua
1 Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Yanbian University, Yanji, China.
2 Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China.
Tumour Biol. 2017 Jul;39(7):1010428317709675. doi: 10.1177/1010428317709675.
Emerging evidence has demonstrated that the high expression of HBXIP has been correlated with many cancers. With evaluation of the functional role of HBXIP in non-small-cell lung cancer, the primary aim of this study is to investigate the correlation between HBXIP expression and the prognosis of non-small-cell lung cancer patients. The protein levels of HBXIP were detected using western blotting in non-small-cell lung cancer cells. Cell proliferation and migration assays were measured to evaluate the function of HBXIP in non-small-cell lung cancer cells. A total of 120 non-small-cell lung cancer patients with strict follow-up and 60 adjacent non-tumor lung tissues were selected for immunohistochemical staining of the HBXIP protein. The localization of the HBXIP protein was detected in A549 non-small-cell lung cancer cells using immunofluorescence staining. The correlation between HBXIP expression and the clinicopathological features of non-small-cell lung cancer patients was analyzed by a chi-squared and Fisher's exact test. The overall survival rates of all of the non-small-cell lung cancer patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In function, we showed that suppression of HBXIP decreased A549 cell proliferation and migration. HBXIP protein showed a mainly cytoplasmic staining pattern in non-small-cell lung cancer using immunohistochemical staining in paraffin-embedded non-small-cell lung cancer tissues and immunofluorescence staining in A549 cells. The HBXIP protein had strong positive staining in the non-small-cell lung cancer tissues, which was significantly higher than the percentage of adjacent non-tumor tissues. The overexpression of HBXIP was closely correlated with histological grade, clinical stage, lymph node metastasis, and lower overall survival rates of patients with non-small-cell lung cancer. Moreover, multivariate analysis suggested that HBXIP emerged as a significant independent prognostic factor along with clinical stage in patients with non-small-cell lung cancer. In conclusion, a high level of expression of HBXIP is associated with the progression of non-small-cell lung cancer and may be a useful biomarker for poor prognostic evaluation and a potential molecular therapy target for patients with non-small-cell lung cancer.
新出现的证据表明，HBXIP的高表达与多种癌症相关。在评估HBXIP在非小细胞肺癌中的功能作用时，本研究的主要目的是探讨HBXIP表达与非小细胞肺癌患者预后之间的相关性。采用蛋白质印迹法检测非小细胞肺癌细胞中HBXIP的蛋白水平。通过细胞增殖和迁移实验来评估HBXIP在非小细胞肺癌细胞中的功能。选取120例有严格随访记录的非小细胞肺癌患者及60例癌旁非肿瘤肺组织进行HBXIP蛋白的免疫组织化学染色。采用免疫荧光染色法检测A549非小细胞肺癌细胞中HBXIP蛋白的定位。采用卡方检验和Fisher精确检验分析HBXIP表达与非小细胞肺癌患者临床病理特征之间的相关性。采用Kaplan-Meier法计算所有非小细胞肺癌患者的总生存率，并使用Cox比例风险回归模型进行单因素和多因素分析。在功能方面，我们发现抑制HBXIP可降低A549细胞的增殖和迁移。在石蜡包埋的非小细胞肺癌组织中进行免疫组织化学染色以及在A549细胞中进行免疫荧光染色，结果显示HBXIP蛋白在非小细胞肺癌中主要呈细胞质染色模式。HBXIP蛋白在非小细胞肺癌组织中呈强阳性染色，显著高于癌旁非肿瘤组织的阳性率。HBXIP的过表达与非小细胞肺癌患者的组织学分级、临床分期、淋巴结转移及较低的总生存率密切相关。此外，多因素分析表明，在非小细胞肺癌患者中，HBXIP与临床分期一样，是一个显著的独立预后因素。总之，HBXIP的高表达与非小细胞肺癌的进展相关，可能是不良预后评估的有用生物标志物，也是非小细胞肺癌患者潜在的分子治疗靶点。
