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ERCC1、TYMS、RRM1、TUBB3、非肌肉肌球蛋白II、肌红蛋白和MyoD1在肺腺癌胸腔积液中的表达可预测接受铂类化疗患者的生存期。

Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy.

作者信息

Jiang Haijiao, Wang He, Wang Shiyu, Pei Zhengtong, Fu Zhimin, Fang Changqing, Wang Jian, Lu Qingjie, Wang Enhua, Li Jianhua

机构信息

Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.

Department of Pathology and Lab Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.

出版信息

Mol Med Rep. 2015 May;11(5):3523-32. doi: 10.3892/mmr.2014.3141. Epub 2014 Dec 30.

Abstract

The association between the expression of excision repair cross‑complementing gene 1 (ERCC1), thymidylate synthase (TYMS), ribonuleotide reductase M1 (RRM1), βIII‑tubulin (TUBB3), non‑muscle myosin II, myoglobin and MyoD1 in metastatic lung adenocarcinoma, and clinical outcomes with platinum‑based chemotherapy treatment is not well‑established. Recently, increasing attention has been focused on the involvement of ERCC1, TYMS, RRM1 and TUBB3 in the development of drug resistance. There has been less research into the role of muscle myosin II, myoglobin and MyoD1 in the pathogenesis of lung cancer, although these genes are known to have important functions within tumor cells. In the current study, malignant pleural effusion from 116 patients with untreated lung adenocarcinoma diagnosed between 2011 and 2012, were collected. The protein expression levels of ERCC1, TYMS, RRM1 and TUBB3 were evaluated with immunocytochemistry and western blot analysis. The expression levels of non‑muscle myosin II, myoglobin and MyoD1 were measured in a subset of 50 patients, treated with platinum‑based chemotherapy. The association of each of these seven factors with one another, as well as with patient survival were analyzed. Immunohistochemistry demonstrated that the percentage of pleural fluid samples from patients with lung adenocarcinoma expressing ERCC1, TYMS, RRM1 and TUBB3 was 37, 36.2, 82.7 and 69.8%, respectively. In the subset of 50 patients in whom the remaining factors were analyzed, the percentage expressing non‑muscle myosin II was 48%, for myoglobin the figure was 40% and for MyoD1 it was 38%. There was a positive correlation between each pair of the above seven molecules with the exception of TYMS and RRM1. Expression of ERCC1, TYMS, TUBB3, non‑muscle myosin II, myoglobin and MyoD1 genes was associated with decreased survival in patients with metastatic lung adenocarcinoma. Expression of ERCC1, TYMS, TUBB3, non‑muscle myosin II, myoglobin and MyoD1 was also associated with decreased survival rates of patients with lung adenocarcinoma treated with platinum‑based chemotherapy. These factors may be used as clinical biomarkers to predict the biological behavior and chemoresistance of tumor cells, and the survival of patients with lung carcinoma.

摘要

切除修复交叉互补基因1(ERCC1)、胸苷酸合成酶(TYMS)、核糖核苷酸还原酶M1(RRM1)、βIII-微管蛋白(TUBB3)、非肌肉肌球蛋白II、肌红蛋白和MyoD1在转移性肺腺癌中的表达与铂类化疗的临床疗效之间的关联尚未明确确立。最近,人们越来越关注ERCC1、TYMS、RRM1和TUBB3在耐药性发展中的作用。尽管已知肌肉肌球蛋白II、肌红蛋白和MyoD1在肿瘤细胞内具有重要功能,但关于它们在肺癌发病机制中的作用的研究较少。在本研究中,收集了2011年至2012年间确诊的116例未经治疗的肺腺癌患者的恶性胸腔积液。采用免疫细胞化学和蛋白质印迹分析评估ERCC1、TYMS、RRM1和TUBB3的蛋白表达水平。在接受铂类化疗的50例患者亚组中检测非肌肉肌球蛋白II、肌红蛋白和MyoD1的表达水平。分析了这七个因素之间以及与患者生存的关联。免疫组织化学显示,肺腺癌患者胸腔积液样本中表达ERCC1、TYMS、RRM1和TUBB3的百分比分别为37%、36.2%、82.7%和69.8%。在分析其余因素的50例患者亚组中,表达非肌肉肌球蛋白II的百分比为48%,肌红蛋白为40%,MyoD1为38%。除TYMS和RRM1外,上述七个分子两两之间均呈正相关。ERCC1、TYMS、TUBB3、非肌肉肌球蛋白II、肌红蛋白和MyoD1基因的表达与转移性肺腺癌患者的生存率降低相关。ERCC1、TYMS、TUBB3、非肌肉肌球蛋白II、肌红蛋白和MyoD1的表达也与接受铂类化疗的肺腺癌患者的生存率降低相关。这些因素可作为临床生物标志物,用于预测肿瘤细胞的生物学行为和化疗耐药性以及肺癌患者的生存情况。

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