High nuclear/cytoplasmic ratio of Cdk1 expression predicts poor prognosis in colorectal cancer patients

Abstract

Background: Cdk1 (cyclin-dependent kinase 1) is critical regulator of the G2-M checkpoint. Cyclin-dependent kinase pathways are considered possible targets for cancer treatment; however, the prognostic role of Cdk1 in colorectal cancer is still controversial. Therefore, we attempted to determine the impact of Cdk1 on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer.

Methods: Cdk1 immunoreactivity was analyzed by immunohistochemistry (IHC) in 164 cancer specimens from primary colorectal cancer patients. The medium follow-up time after surgery was 3.7 years (range: 0.01 to 13.10 years). The prognostic value of Cdk1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models.

Results: All samples displayed detectable Cdk1 expression with predominant location in the cytoplasm and nucleus. A high Cdk1 nuclear/cytoplasmic (N/C) expression ratio was correlated with poor overall survival (5-year survival rate: 26.3% vs 46.9%, N/C ratio ≥1.5 vs N/C ratio <1.5, log-rank p = 0.027). Accordingly, a Cdk1 N/C expression ratio ≥1.5 was identified as an independent risk factor by multivariate analysis (hazard ratio = 1.712, P = 0.039).

Conclusions: We suggest that Cdk1 N/C expression ratio determined by IHC staining could be an independent prognostic marker for colorectal cancer.

Figure 1

Representative immunostaining of Cdk1 in colorectal cancer in tissue arrays according to the N/C ratio. N/C ratio of Cdk1 were (A) 0.00-0.49; (B) 0.50-0.99; (C) 1.00-1.49; (D) ≥1.5. (Magnification: 200×).

Figure 2

A high Cdk1 N/C ratio was correlated with poor overall survival. Kaplan-Meier actuarial analysis of overall survival according to (A) N/C ratio subgroups and (B) N/C ratio cut by 1.5 of Cdk1 immunostaining expression in colorectal cancer patients. The case number was 18, 101, 26, and 19 according to N/C ratio subgroups, respectively.