ABSTRACT
Colorectal cancer has a common cause of morbidity and mortality. Therefore, it is urgent to detect reliable biomarkers to predict prognosis in CRC. Here, we determined the expression of TIMP-2 and MMP-9 in a CRC tissue microarray by immunohistochemistry. We found that lower TIMP-2 or/and higher MMP-9 expression in cancer tissues was correlated with poorer overall survival (OS). TIMP-2 or MMP-9 expression was independent prognostic factors for CRC. Furthermore, TIMP-2 and MMP-9 expression had a synergistic role as efficient prognostic indicators for CRC patients. In vitro and in vivo, TIMP-2 could inhibit HCT 116 cells invasion and migration by regulating MMP-9. In sum, a combined expression of TIMP-2 and MMP-9 as efficient prognostic indicators was found for the first time.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , Matrix Metalloproteinase 9/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Aged , Cell Line, Tumor , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Female , HCT116 Cells , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/pathology , Neovascularization, Pathologic/pathology , PrognosisABSTRACT
PURPOSE: To investigate the precise function of Cullin1 (CUL1) in colorectal cancer (CRC). METHODS: Immunohistochemistry was performed to test the expression of CUL1 on a CRC tissue microarray containing the tumor and corresponding normal tissues. Simultaneously, the correlation of CUL1 expression with clinicopathological parameters and survival was evaluated. CUL1 was over-expressed or knocked down in HCT116 and SW480 cells, then the cell proliferation, migration and invasion assays in vitro and in vivo were performed. RESULTS: In this study, we found that CUL1 expression was significantly up-regulated in CRC compared with normal colon tissues. High CUL1 expression was positively associated with lymph node metastasis (P = 0.007) and tumor diameter (P = 0.052). Multivariate Cox regression analysis revealed that high CUL1 expression was an independent unfavorable prognostic factor for CRC patients (HR = 13.9, 95% confidence interval = 5.89-32.6, P < 0.001). Moreover, we found that CUL1 over-expression induced CRC cell proliferation and the growth of xenografts in nude mice via the changing of cell-cycle proteins. In addition, increased CUL1 expression in CRC cells significantly promoted cell migration and invasion abilities in vitro and peritoneal metastasis in vivo through inducing high expression of MMPs. CONCLUSION: Our findings imply that CUL1 may serve as promising prognostic markers in CRC patients.
