Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer

Abstract

Background: Cdc7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms and cancer progression. Recently, it has been suggested as a target for anti-cancer therapy.

Methods: To determine the relationship of Cdc7 protein expression with tumor phenotype, molecular features and prognosis, 1800 colorectal carcinomas were analyzed by immunohistochemistry on a tissue microarray.

Results: Cdc7 expression was considered negative in 33.6%, weak in 57.2% and strong in 9.2% of 1711 interpretable CRCs. Loss of Cdc7 expression was significantly associated with high tumor stage (p < 0.0001) and high tumor grade (p = 0.0077), but was unrelated to the nodal status (p = 0.5957). Moreover, a link between Cdc7 expression and the tubular histological tumor type was seen (p < 0.0001). p53 and Cdc7 expression were significantly linked to each other (p = 0.0013). In a multivariate survival analysis, strong Cdc7 expression of CRC was an independent marker of improved patient survival (p = 0.0031).

Conclusion: Our data show that Cdc7 is highly expressed in CRC and a potential therapeutic target in a subset of cancers with high p53 expression. Moreover, our findings strongly argue for a clinical utility of Cdc7 immunostaining as an independent prognostic biomarker in colorectal cancer enabling to select patients for adjuvant treatment.

Fig. 1

Representative images of immunohistochemical Cdc7 and p53 expression in colorectal cancer: a Cdc7 negative; b Cdc7 low and c Cdc7 high expression, d p53 negative; e p53 low and f p53 high expression, magnification 50 x each

Fig. 2

Association between survival and a Tumor stage, p < 0.0001; b Nodal status, p < 0.0001; c Tumor grade, p < 0.0001 and d Cdc7 expression (Cdc7 strong-blue, Cdc7 weak-green, Cdc7-negative-red); p = 0.0003