Abstract
BackgroundCHCHD2 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.MethodsIn 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.ResultsData 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).ConclusionOur 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.
Highlights
Coiled-coil-helix-coiled-coil-helix domaincontaining protein 2 (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 Oxidative phosphorylation (OxPhos) function as well
CHCHD2 and HIF-1α overexpressed in non-small-cell lung cancer (NSCLC) tissue We collected 12 paired fresh tumor and normal tissue samples, CHCHD2 and HIF-1a mRNA and protein expression levels in those tissues were detected by qRTPCR and Western blot respectively
High levels of CHCHD2, HIF-1α predict poor prognosis of NSCLC patients In order to explore whether the expression of CHCHD2 and HIF-1a are prognostic factors for NSCLC, we investigate the correlation between the expressions of CHCHD2 and HIF-1a and patient survival
Summary
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. We assumed that CHCHD2 expression would accompanies the expression of HIF-1α to response hypoxia in the occurrence of NSCLC. Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide [1]. As lung cancer cells infiltrate into surrounding tissue and metastasize to distant organs, the 5-year survival rate in lung cancer patients was very low. In spite of improvements in surgical, radiotherapy, platinum-based doublet chemotherapy and recently developed targeted therapies [5], the prognosis of NSCLC is still very poor and about 30–55% of the patients who are diagnosed early and treated by surgery will develop a recurrence [6, 7]. The targeted therapies interrupt signaling pathways which responsible for lung cancer cell proliferation and survival [5]. It is urgent to understand the potential molecular mechanisms mediating the NSCLC tumorigenesis and identify novel biomarkers to help provide individualization treatment and assess better prognosis [8, 9]
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