Effects of p38MAPK-mediated excision repair cross-complementation 1 expression on prognosis of patients with non-small cell lung cancer.

Effects of p38MAPK-mediated excision repair cross-complementation 1 expression on prognosis of patients with non-small cell lung cancer.
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p38MAPK介导的切除修复交叉互补1表达对非小细胞肺癌患者预后的影响

DOI:
10.3892/ol.2017.6649
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发表时间:
2017-09
期刊:
影响因子:
2.9
通讯作者:
Sun W
Sun W
中科院分区:
医学4区
文献类型:
--
作者:
He D;Ma X;Wu Z;Wang Y;Zhao S;Han F;Sun W

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本研究旨在探讨切除修复交叉互补基因1(ERCC1)的表达对非小细胞肺癌(NSCLC)患者预后的影响。共纳入140例行根治性切除术的NSCLC患者。对患者获取的组织标本进行免疫组织化学染色,并采用相关性分析确定ERCC1表达与临床病理特征之间的关联。使用MTT法评估细胞增殖情况。分别采用逆转录 - 定量聚合酶链反应和蛋白质免疫印迹分析检测mRNA和蛋白质表达水平。结果显示,与癌旁组织样本相比,肿瘤组织中ERCC1的表达显著升高。此外,鳞状细胞癌中ERCC1的表达明显高于腺癌样本。吸烟患者的ERCC1表达显著高于不吸烟患者。ERCC1阴性患者的3年无病生存率(DFS)和总生存率(OS)高于ERCC1阳性患者。多因素分析表明,ERCC1表达、病理分期和肿瘤分期是NSCLC的重要预后因素。亚组分析显示,接受系统辅助化疗的Ⅱ - Ⅲ期肿瘤且ERCC1阴性患者的3年总生存率高于ERCC1阳性患者。鳞状细胞癌且ERCC1阴性患者的3年无病生存率和总生存率高于ERCC1阳性患者。此外,p38抑制剂处理显著抑制A549细胞中ERCC1的mRNA和蛋白质表达水平,并增强了细胞对顺铂的敏感性。本研究结果表明,ERCC1表达是NSCLC的重要预后指标,尤其对于接受系统铂类辅助化疗的Ⅱ - Ⅲ期肿瘤患者。
The present study aimed to investigate the effects of excision repair cross-complementation 1 (ERCC1) expression on the prognosis of patients with non-small cell lung cancer (NSCLC). A total of 140 patients with NSCLC who underwent radical resection were included. Immunohistochemical staining was performed on the tissue specimens obtained from patients and correlation analysis was used to determine the association between ERCC1 expression and clinicopathological characteristics. Cell proliferation was assessed using an MTT assay. The mRNA and protein expression levels were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The expression of ERCC1 was demonstrated to be significantly elevated in tumor tissue compared with adjacent tissue samples. Furthermore, the expression of ERCC1 in squamous carcinoma was significantly higher compared with in adenocarcinoma samples. The expression of ERCC1 in patients who smoke was significantly higher compared with in the non-smokers. The 3-year disease-free survival (DFS) and overall survival (OS) for ERCC1-negative patients were higher compared with ERCC1-positive patients. Multivariate analysis demonstrated that ERCC1 expression, pathological staging, and tumor staging were important prognostic factors for NSCLC. Subgroup analysis revealed that the 3-year OS rate for ERCC1-negative patients with stage II–III tumors who received systematic adjuvant chemotherapy was higher compared with ERCC1-negative patients. The 3-year DFS and OS rates for ERCC1-negative patients with squamous carcinoma were higher compared with ERCC1-positive patients. In addition, p38 inhibitor treatment significantly inhibited the mRNA and protein expression levels of ERCC1 in A549 cells, and enhanced the sensitivity of cells to cisplatin. The results of the present study suggest that ERCC1 expression is an important prognostic indicator for NSCLC, particularly for patients with stage II–III tumors who receive systematic platinum-based adjuvant chemotherapy.
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