title: The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer.
  
  
  METHODS
  Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining.
  
  
  RESULTS
  In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10(-5) and P = 2.8 × 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10(-5) and P = 1.6 × 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232).
  
  
  CONCLUSIONS
  The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Dianshui
authors: D
authors: Sun
authors: Medical Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.
authors: Xin
authors: X
authors: Li
authors: Pathology Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.
authors: Maoqiang
authors: M
authors: Ma
authors: Department of Thoracic Surgery, Shandong Institute for Cancer Research, Jinan, China.
authors: Jie
authors: J
authors: Liu
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Ying
authors: Y
authors: Xu
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Lan
authors: L
authors: Ye
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Huaying
authors: H
authors: Hou
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Cuihong
authors: C
authors: Wang
authors: Cancer Center, The Second Hospital of Shandong University, Jinan.
authors: Xiaomei
authors: X
authors: Li
authors: Cancer Center, The Second Hospital of Shandong University, Jinan xm_sduniversity@163.com.
authors: Yuhua
authors: Y
authors: Jiang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000556:secondary*; D015820:Cadherins / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D011237:Predictive Value of Tests; D051571:Protein Kinase C-alpha / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit / Q000032:analysis; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D035683:MicroRNAs; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051571:Protein Kinase C-alpha
keywords: brain metastases; miRNA-328; miRNA-378; non-small-cell lung cancer; predictive value