BACKGROUND CHCHD2 was identified a novel cell migration-promoting gene, which could promote cell migration and altered cell adhesion when ectopically overexpressed in NIH3T3 fibroblasts, and it was identified as a protein necessary for OxPhos function as well. However, the clinic relevance of CHCHD2 expression in NSCLC remains unclear. Here we assumed that CHCHD2 expression would accompanies the expression of HIF-1α to response hypoxia in the occurrence of NSCLC. METHODS In order to verify this hypothesis, correlations among the expression levels of CHCHD2 and HIF-1α were detected and analyzed in 209 pair cases of NSCLC. The expression and location of these molecules were assessed using Immunohistochemistry, immunohistofluorescence, qRT-PCR and western blotting. The differences and correlations of the expression of these two molecules with clinical pathological characteristics in NSCLC were statistically analyzed using Wilcoxon (W) text, Mann-Whitney U, Kruskal-Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of the expression of CHCHD2 and HIF-1α on the patients' survival. RESULTS Data showed that CHCHD2 and HIF-1α expression were higher in NSCLC than in normal tissues (all P = 0.000). CHCHD2 expression was significantly related with smoking, tumor size, differentiation degree, TNM Stage, lymph metastasis (all P<0.05). The HIF-1α expression was significantly associated with smoking, tumor category, differentiation degree, TNM Stage, Lymph metastasis (all P<0.05). There was a marked correlation of CHCHD2 and HIF-1α expression with histological type, differentiation and lymph metastasis of NSCLC (all P<0.05, rs>0.3). Immunohistofluorescence showed that there were co-localization phenomenon in cytoplasm and nucleus between CHCHD2 and HIF-1α expression. NSCLC patients with higher CHCHD2 and HIF-1α expression had a significantly worse prognosis than those with lower CHCHD2 and HIF-1α expression (all P = 0.0001; log-rank test). The multivariate analysis indicated that CHCHD2 expression was an independent prognostic factor in NSCLC (hazard ratio [HR], 0.492, P = 0.001). CONCLUSION Our results indicate that over-expression of CHCHD2 would promote the expression of HIF-1α to adapt the hypoxia microenviroment in NSCLC and CHCHD2 could serves as a prognostic biomarker in NSCLC.

中文翻译：

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CHCHD2是NSCLC的潜在预后因素，并与HIF-1a表达相关。

背景技术CHCHD2被鉴定为一种新型的细胞迁移促进基因，当在NIH3T3成纤维细胞中异位过表达时，它可以促进细胞迁移并改变细胞粘附，并且被鉴定为OxPhos功能所必需的蛋白质。但是，尚不清楚NSCLC中CHCHD2表达的临床相关性。在这里，我们假设CHCHD2表达将伴随HIF-1α的表达，以响应NSCLC发生时的缺氧。方法为了验证这一假设，在209对非小细胞肺癌中检测并分析了CHCHD2和HIF-1α表达水平之间的相关性。使用免疫组织化学，免疫组织荧光，qRT-PCR和蛋白质印迹法评估这些分子的表达和位置。使用Wilcoxon（W）文本，Mann-Whitney U，Kruskal-Wallis H和交叉表检验对这两种分子在NSCLC中具有临床病理特征的表达差异和相关性进行统计分析。用Kaplan-Meier生存分析和Cox比例风险模型评估CHCHD2和HIF-1α表达对患者生存的影响。结果数据显示，NSCLC中CHCHD2和HIF-1α的表达高于正常组织（所有P = 0.000）。CHCHD2的表达与吸烟，肿瘤大小，分化程度，TNM分期，淋巴转移密切相关（均P <0.05）。HIF-1α表达与吸烟，肿瘤分类，分化程度，TNM分期，淋巴结转移密切相关（均P <0.05）。CHCHD2和HIF-1α的表达与NSCLC的组织学类型，分化和淋巴转移有显着相关性（均P <0.05，rs> 0.3）。免疫组织荧光显示CHCHD2和HIF-1α表达在细胞质和细胞核中存在共定位现象。CHCHD2和HIF-1α表达较高的NSCLC患者的预后明显低于CHCHD2和HIF-1α表达较低的患者（所有P = 0.0001；对数秩检验）。多元分析表明，CHCHD2表达是NSCLC的独立预后因素（危险比[HR]为0.492，P = 0.001）。结论我们的结果表明，CHCHD2的过表达将促进HIF-1α的表达以适应NSCLC中的缺氧微环境，而CHCHD2可以作为NSCLC中的预后生物标志物。