Upregulation of circulating cytokeratin 20, urokinase plasminogen activator and C-reactive protein is associated with poor prognosis in gastric cancer.

Abstract

Gastric cancer is one of the most common types of cancer, with a high mortality rate. The aim of this study was to investigate the role of several key molecules, including cytokeratin (CK) 19 and CK20, urokinase plasminogen activator (uPA), C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9, which are involved in cancer invasion and metastasis, in order to determine whether they may be considered as novel prognostic factors for gastric cancer. Peripheral blood was collected from 165 patients with gastric adenocarcinoma who underwent curative surgical resection at Zhejiang Cancer Hospital (Hangzhou, China) between 2010 and 2011. The mRNA levels of CK19, CK20, uPA and MMP-9 were detected by reverse transcription-quantitative polymerase chain reaction. The protein expression of CRP was measured by immunoturbidimetry. The Students t-test was used in the univariate analyses and the Kaplan-Meier method was used to analyze the survival curves. The relative mRNA expression of CK19 and MMP-9 was not found to be significantly associated with gender, age or cancer stage, whereas that of CK20 and uPA was associated with gastric cancer stage: The low-expression group was associated with early-stage and the high-expression group with more advanced-stage disease (P<0.05). The CRP protein level was associated with gender and cancer stage: The low-expression group was predominantly associated with male gender and early-stage disease, whereas the high-expression group was associated with female gender and advanced-stage disease (P<0.05). The expression of CK19, CK20, uPA and CRP, but not MMP-9, was negatively associated with overall survival (OS): The OS rate in the high-expression groups was significantly lower compared with that in the low-expression groups (P<0.05). In conclusion, the upregulation of CK20, uPA and CRP was found to be a negative prognostic factor for gastric cancer.