title: Significance of BMI1 and FSCN1 expression in colorectal cancer.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and the fourth in cause of death world-wide, underscoring the need to identify novel biomarkers for early diagnosis, as well as improved disease stratification and treatment choices.
  
  
  METHODS
  The Gene Expression Omnibus (GSE21510) and the Cancer Genome Atlas (TCGA) CRC datasets were utilized in the current study. GeneSpring 13.0 was used for normalization and analysis. The log-rank test was used to compare the outcome between expression groups.
  
  
  RESULTS
  Significant upregulation of BMI1 (2.3 FC, P = 3.7 × 10-18) and FSCN1 (1.3 FC,P = 4.7 × 10-3) was observed in CRC. High BMI1 expression was associated with reduced overall survival (OS) [Hazard ratio (HR), 1.87; 95% CI. 1.17-3.03; P= 0.009] and reduced disease-free survival (DFS) [HR, 162; 95% CI 1.01-2.63;P = 0.045]. Similarly, high expression of FSCN1 was associated with reduced OS (HR, 2.0; 95% CI, 1.24-3.2; P= 0.0044) and reduced DFS (HR, 1.60; 95% CI, 0.99-2.57;P = 0.055). Importantly, BMI1high/FSCN1high patients experienced the worst OS (HR, 3.17; 95% CI, 1.77-6.15; P= 0.0002) and DFS (HR, 2.34; 95% CI, 1.27-4.67,P = 0.0078). Using pathway analyses, tumors overexpressing BMI1 were enriched in zinc finger proteins and genes involved in DNA binding and regulation of transcription, whereas tumors expressing FSCN1 were enriched in genes involved in cell migration.
  
  
  CONCLUSIONS
  Our data revealed poor OS and DFS in CRC patients overexpressing BMI1 or FSCN1 and suggest that these two markers in combination may represent superior prognostic marker to either one. Targeting BMI1 and FSCN1 may also provide potential therapeutic opportunity in CRC.
authors.affiliation: Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh - 11461, Kingdom of Saudi Arabia.
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D015854:Up-Regulation
chemical_list: C069077:BMI1 protein, human; D002352:Carrier Proteins; C502658:FSCN1 protein, human; D008840:Microfilament Proteins; D063150:Polycomb Repressive Complex 1