Significance of BMI1 and FSCN1 Expression in Colorectal Cancer

Background/Aims: 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. Patients and 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. Result: Significant upregulation of BMI1 (2.3 FC, P = 3.7 x 10(-18)) and FSCN1 (1.3 FC, P = 4.7 x 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, BMI1(high)/FSCN1(high) 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. Conclusion: 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.