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维甲酸相关孤儿受体C亚型2在非小细胞肺癌中的表达及其预后意义

Retinoic acid-related orphan receptor C isoform 2 expression and its prognostic significance for non-small cell lung cancer.

作者信息

Huang Qi, Fan Jinshuo, Qian Xin, Lv Zhilei, Zhang Xiuxiu, Han Jieli, Wu Feng, Chen Caiyun, Du Jiao, Guo Mengfei, Hu Guorong, Jin Yang

机构信息

Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of the Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People's Republic of China.

Department of Respiratory Medicine, Taihe Hospital, Hubei University of Medicine, No. 98 South Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2016 Jan;142(1):263-72. doi: 10.1007/s00432-015-2040-0. Epub 2015 Aug 30.

Abstract

BACKGROUND

Retinoic acid-related orphan receptor C isoform 2 (RORC2) is regarded as a pathogenic factor for autoimmune and inflammatory diseases and tumours. Previous studies have primarily focused on RORC2 expression in IL-17-producing immune cells but not in carcinoma cells; thus, little is known about the roles of RORC2 in the progression of human non-small cell lung cancer (NSCLC). In this study, we analysed the expression of RORC2 and its participation in tumour progression in NSCLC.

METHODS

RORC2 expression in NSCLC and adjacent normal lung tissues was assessed via quantitative real-time PCR (qRT-PCR) and immunohistochemistry. RORC2 expression in NSCLC cell lines was examined by qRT-PCR, Western blotting and flow cytometry. The effects of inhibiting RORC2 activity on the proliferation of NSCLC cells were evaluated. The prognostic value of RORC2 for NSCLC was revealed based on Kaplan-Meier analysis.

RESULTS

High RORC2 expression was observed in lung cancer tissues and was significantly related to age (p = 0.013) and regional lymph node metastasis (p = 0.009). RORC2 expression was higher in the A549, H460, SPC-A1 and H1299 cell lines than in a control cell line. In addition, cell proliferation was decreased in NSCLC cells upon the blocking of RORC2 activity using a specific inhibitor. High RORC2 expression correlated with worse overall survival (p = 0.030).

CONCLUSIONS

Our study suggests that RORC2 is expressed by lung cancer cells and greatly contributes to tumour cell proliferation and overall survival in NSCLC. These findings strongly imply that RORC2 is associated with tumour progression.

摘要

背景

维甲酸相关孤儿受体C亚型2(RORC2)被认为是自身免疫性疾病、炎症性疾病和肿瘤的致病因素。以往的研究主要集中在RORC2在产生白细胞介素-17的免疫细胞中的表达,而非癌细胞中的表达;因此,对于RORC2在人类非小细胞肺癌(NSCLC)进展中的作用知之甚少。在本研究中,我们分析了RORC2的表达及其在NSCLC肿瘤进展中的参与情况。

方法

通过定量实时聚合酶链反应(qRT-PCR)和免疫组织化学评估NSCLC及邻近正常肺组织中RORC2的表达。通过qRT-PCR、蛋白质免疫印迹法和流式细胞术检测NSCLC细胞系中RORC2的表达。评估抑制RORC2活性对NSCLC细胞增殖的影响。基于Kaplan-Meier分析揭示RORC2对NSCLC的预后价值。

结果

在肺癌组织中观察到RORC2高表达,且与年龄(p = 0.013)和区域淋巴结转移(p = 0.009)显著相关。RORC2在A549、H460、SPC-A1和H1299细胞系中的表达高于对照细胞系。此外,使用特异性抑制剂阻断RORC2活性后,NSCLC细胞的增殖减少。RORC2高表达与较差的总生存期相关(p = 0.030)。

结论

我们的研究表明,RORC2由肺癌细胞表达,并在很大程度上促进NSCLC中的肿瘤细胞增殖和总生存期。这些发现强烈表明RORC2与肿瘤进展相关。

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