Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer
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Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer. / Melling, Nathaniel; Muth, Johanna; Simon, Ronald; Bokemeyer, Carsten; Terracciano, Luigi; Sauter, Guido; Izbicki, Jakob Robert; Marx, Andreas Holger.
In: DIAGN PATHOL, Vol. 10, 2015, p. 125.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer
AU - Melling, Nathaniel
AU - Muth, Johanna
AU - Simon, Ronald
AU - Bokemeyer, Carsten
AU - Terracciano, Luigi
AU - Sauter, Guido
AU - Izbicki, Jakob Robert
AU - Marx, Andreas Holger
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1186/s13000-015-0360-7
DO - 10.1186/s13000-015-0360-7
M3 - SCORING: Journal article
C2 - 26208856
VL - 10
SP - 125
JO - DIAGN PATHOL
JF - DIAGN PATHOL
SN - 1746-1596
ER -
