title: Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients.
abstract: BACKGROUND
  The nuclear localization of Drosha is critical for its function as a microRNA maturation regulator. Dephosphorylation of Drosha at serine 300 and serine 302 disrupts its nuclear localization, and aberrant distribution of Drosha has been detected in some tumors.
  
  
  OBJECTIVE
  The purpose of the present study was to assess cytoplasmic/nuclear Drosha expression in gastric cancer carcinogenesis and progression.
  
  
  METHODS
  Drosha expression and its subcellular location was investigated by immunohistochemical staining of a set of tissue microarrays composed of normal adjacent tissues (374), chronic gastritis (137), precancerous lesions (94), and gastric adenocarcinoma (829) samples, and in gastric cancer cell lines with varying differentiation by immunofluorescence and western blot assay.
  
  
  RESULTS
  Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P < 0.001), tumor stage (P = 0.018), and distant metastasis (P = 0.026). Aberrant high levels of cytoplasmic Drosha were apparent in intestinal metaplasia and dysplasia tissues. The levels of nuclear Drosha were sharply decreased in chronic gastritis and maintained through precancerous lesions to gastric cancer. High levels of cytoplasmic Drosha predicted longer survival (LR = 7.088, P = 0.008) in gastric cancer patients.
  
  
  CONCLUSIONS
  Our data provide novel insights into gastric cancer that cytoplasmic Drosha potentially plays a role in preventing carcinogenesis and tumor progression, and may be an independent predictor of patient outcome.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Experimental Teaching Center of Basic Medicine Science, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Zongyue
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Wen
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yan-E
authors.initials: YE
authors.lastname: Du
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Sun
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Yin
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lang
authors.affiliation: Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. mliu-hncq@hotmail.com.
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000378:metabolism*; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism*; D011379:Prognosis; D043244:Ribonuclease III / Q000378:metabolism*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C517918:DROSHA protein, human; D043244:Ribonuclease III
keywords: Carcinogenesis; Drosha; Gastric cancer; Precancerous lesions; Tumor progression