title: Testicular orphan receptor 4 (TR4) is a marker for metastasis and poor prognosis in non-small cell lung cancer that drives the EMT phenotype.
abstract: OBJECTIVE
  Aberrant expression of testicular orphan receptor 4 (TR4) has been shown to regulate biological processes near solid tumors. However, the role of TR4 in non-small cell lung cancer (NSCLC) patient prognosis and the development of NSCLC cancer cells are unclear.
  
  
  METHODS
  Immunohistochemical analysis was used to evaluate the correlation between TR4 expression and clinicopathological characteristics in 291 cases of NSCLC specimens. A knockdown and overexpression of TR4 was performed to assess the role of TR4. Transwell and colony formation assays were completed to investigate the metastatic and proliferative abilities. Quantitative real-time PCR, Western blotting and immunofluorescence staining were carried out to analyze the epithelial-to-mesenchymal transition (EMT) phenotype.
  
  
  RESULTS
  Immunohistochemical evaluation of clinical samples revealed that most of the lung cancer tissues were strongly positive for TR4, whereas the tissues that stained weakly positive or negative for TR4 expression were shown in the paired normal tissues. Moreover, higher levels of TR4 expression were significantly associated with higher lymph node metastases, TNM stages, tumor thrombus in vena and poor prognosis. We observed that downregulation and up-regulation of TR4 with stable cell transfection significantly influence the proliferation, invasive and metastatic abilities of NSCLC lines. In addition, aberrant TR4 expression could modulate the expression levels of several EMT related markers.
  
  
  CONCLUSIONS
  Collectively, our results show TR4 expression in NSCLC samples is significantly associated with poor clinicopathological features, and TR4 plays an important role in the metastatic capacity of NSCLC cells by EMT regulation.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Cell Biology, Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Qinfeng
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Beijing, People's Republic of China. Electronic address: zlyangyue@bjmu.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D057125:Nuclear Receptor Subfamily 2, Group C, Member 2 / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D057125:Nuclear Receptor Subfamily 2, Group C, Member 2
keywords: EMT; Immunohistochemistry; Metastasis; NSCLC; Prognosis; Testicular orphan receptor 4