Alajez Nehad M
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh - 11461, Kingdom of Saudi Arabia.
Saudi J Gastroenterol. 2016 Jul-Aug;22(4):288-93. doi: 10.4103/1319-3767.187602.
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.
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.
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.
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.
背景/目的：结直肠癌（CRC）在全球范围内的发病率是第三大常见癌症类型，在死因方面位列第四，这凸显了识别用于早期诊断的新型生物标志物以及改善疾病分层和治疗选择的必要性。
本研究使用了基因表达综合数据库（GSE21510）和癌症基因组图谱（TCGA）的CRC数据集。使用GeneSpring 13.0进行标准化和分析。采用对数秩检验比较表达组之间的结果。
在CRC中观察到BMI1（2.3倍变化，P = 3.7×10-18）和FSCN1（1.3倍变化，P = 4.7×10-3）显著上调。高BMI1表达与总生存期（OS）降低相关[风险比（HR），1.87；95%置信区间（CI），1.17 - 3.03；P = 0.009]以及无病生存期（DFS）降低相关[HR，1.62；95% CI，1.01 - 2.63；P = 0.045]。同样，FSCN1高表达与OS降低相关（HR，2.0；95% CI，1.24 - 3.2；P = 0.0044）以及DFS降低相关（HR，1.60；95% CI，0.99 - 2.57；P = 0.055）。重要的是，BMI1高/FSCN1高的患者经历了最差的OS（HR，3.17；95% CI，1.77 - 6.15；P = 0.0002）和DFS（HR，2.34；95% CI，1.27 - 4.67，P = 0.;0078）。通过通路分析，过表达BMI1的肿瘤在锌指蛋白以及参与DNA结合和转录调控的基因中富集，而过表达FSCN1的肿瘤在参与细胞迁移的基因中富集。
我们的数据显示，过表达BMI1或FSCN1的CRC患者的OS和DFS较差，提示这两种标志物联合可能代表比单一标志物更优的预后标志物。靶向BMI1和FSCN1也可能为CRC提供潜在的治疗机会。
