title: Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma.
abstract: BACKGROUND
  MicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC.
  
  
  METHODS
  miR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay.
  
  
  RESULTS
  The expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival.
  
  
  CONCLUSIONS
  This study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC.
authors.affiliation: Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Hong-Hua
authors.initials: HH
authors.lastname: Peng
authors.forename: Yang-de
authors.initials: YD
authors.lastname: Zhang
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Gong
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
keywords: microRNA-335; primary gallbladder carcinoma; prognosis; real-time quantitative RT-PCR assay