title: Msi-1 is a predictor of survival and a novel therapeutic target in colon cancer.
abstract: BACKGROUND
  Musashi1 (Msi-1), a neural RNA-binding protein, plays an important role in regulating cell differentiation in precursor cells. Recently, aberrant expression of Msi-1 has been detected in several malignancies. However, its role in the progression of colon cancer is largely unknown.
  
  
  METHODS
  We used Western blotting to examine Msi-1 protein expression in 8 cases of primary colon cancer lesions and paired normal colonic mucosa. Msi-1 expression and clinicopathological significance were determined by immunohistochemical staining in a tissue microarray (TMA) containing 203 cases of primary colon cancer paired with noncancerous tissue and 66 lymph node metastasis (LNM) tissues. RNAi was used to analyze the biological function of Msi-1 in vitro.
  
  
  RESULTS
  LNM tissue exhibited a striking increase in Msi-1 expression when compared with primary colon cancer and adjacent normal mucosa (87.9% vs. 64.5% vs. 16.7%, P < .001). Overexpression of Msi-1 was associated with higher clinical stage, T stage, lymph node metastasis, presence of distant metastasis, and Ki-67 positivity. Msi-1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) (HR 5.4; P < .001) and poorer overall survival (OS) (HR 3.8; P < .001). Msi-1 silencing significantly inhibited proliferation ability and attenuated the migration and invasion activity of colon cancer cells.
  
  
  CONCLUSIONS
  Our study provides the basis to explore the use of Msi-1 as a novel prognostic biomarker in colon cancer patients. Aberrant overexpression of Msi-1 during metastasis of colon cancer also suggests that it is a potential therapeutic target.
authors: Department of General Surgery, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors: Dawei
authors: D
authors: Li
authors: Xiao
authors: X
authors: Peng
authors: Dongwang
authors: D
authors: Yan
authors: Huamei
authors: H
authors: Tang
authors: Fei
authors: F
authors: Huang
authors: Yinxue
authors: Y
authors: Yang
authors: Zhihai
authors: Z
authors: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins