title: Identification and functional characterization of microRNAs reveal a potential role in gastric cancer progression.
abstract: OBJECTIVE
  To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC).
  
  
  METHODS
  We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients' information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity.
  
  
  RESULTS
  22 GC specific key miRNAs were identified (Fold-change >2, P < 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (P < 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank P < 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (P < 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (P < 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same.
  
  
  CONCLUSIONS
  These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Li
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China. lianggeyu@163.com.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Liang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Yao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Sui
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Peng
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: W-W
authors.initials: WW
authors.lastname: Hong
authors.affiliation: Gansu Wuwei Tumor Hospital, Wuwei, 733000, Gansu, People's Republic of China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Ye
authors.affiliation: Gansu Wuwei Tumor Hospital, Wuwei, 733000, Gansu, People's Republic of China.
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Gansu Wuwei Tumor Hospital, Wuwei, 733000, Gansu, People's Republic of China.
authors.forename: W-H
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: L-H
authors.initials: LH
authors.lastname: Yin
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, 87 Dingjiaqiao Street, Nanjing, 210009, Jiangsu, People's Republic of China.
authors.forename: Y-P
authors.initials: YP
authors.lastname: Pu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Clinical features; Gastric cancer; Overall survival; miRNA