Notch1 and Notch2 may be independent adverse prognostic predictors for patients with colorectal cancer. These results would contribute to identify more efficient prognostic predictors and therapeutic targets.

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Matrix metalloproteinase-9 is a member of the Matrix metalloproteinases (MMP) family, which is overexpressed in some solid tumor and thought to enhance the tumor invasion and metastasis ability. Our study is to investigate the association of MMP-9 expression with disease-free survival and overall survival of patients with gastric cancer. Clinical gastric cancer specimens and adjacent normal tissues from 286 patients who had not received neoadjuvant chemotherapy were investigated by immunohistochemistry assay. Staining evaluation results were analyzed statistically in relation to various clinicopathological characters, disease-free survival and overall survival. High level of MMP-9 expression was detected in gastric cancer, significantly more than in adjacent normal epithelial cells. In gastric cancer, MMP-9 was significantly positively correlated with depth of invasion, lymph node metastasis and distant metastasis. However, no correlations between MMP-9 expression and patients' age, sex, tumor location or differentiation status were detected. The disease-free survival and overall survival were significantly shorter for patients with MMP-9 positive than those with MMP-9 negative tumors. Multivariate analysis identified MMP-9 was an independent prognostic factor for both disease-free survival and overall survival. Our findings provided convincing evidence for MMP-9 as an important role in human gastric cancer recurrence and prognosis. It might also serve as a novel target for both prognostic prediction and therapeutics.Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteins that are found in the extracellular milieu of various tissues.1 They are a multigene family of highly homologous enzymes sharing a similar structure, involved in extracellular matrix (ECM) proteins7-10 remodelling processes. 2-5To date, at least 26 known human MMPs have been discovered.6 Based on sequence homology and substrate specificities, the MMPs can be divided into several distinct subclasses: collagenases, gelatinases, stromelysins and matrilysins. 7 MMPs are frequently overexpressed in various human cancers and have long been associated with malignancy. [8][9][10] However, MMPs exhibit considerable promiscuity with respect to their substrates, leading to considerable redundancy in biologic functions, in which the effects on tumor aggressiveness were of vital importance. 11 The development of tumor invasion and metastasis is a complicated and continuous process with multiple steps. To invade and metastasize tumor cells must break through ECM and basement membrane of the epithelium; then infiltrate blood vessels and lymphatics to build up secondary cancer cell colonies at distant sites. There has been a great deal of interest in the role of MMPs in cancer invasion and metastasis due to their ECM degrading capacity.1,2 Thus, MMPs have for long been viewed as key modulators of tumor progression and metastasis. A substantial subsequent study has provided evidence for an association between MMPs expression and tumor aggressive...

The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis. Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation. These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.

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The hepatocellular carcinoma‐associated antigen HAb18G/CD147, a member of CD147 family, could promote tumour invasion and metastasis via inducing the secretion of matrix metalloproteinases (MMP). Anti‐CD147 monoclonal antibodies (MoAb) have exhibited obvious inhibitory effect on MMP induction. However, none of the epitopes of these MoAb has been reported. We previously prepared five MoAb against HAb18G/CD147, named HAb18, 3B3, 1B3, 5A5 and 4D2. To map the epitopes of these MoAb, a series of truncated fragments of extracellular region of HAb18G/CD147 was expressed in Escherichia coli and the MoAb‐binding affinity to these fragments was examined with an enzyme‐linked immunosorbent assay and Western blot. The residues 39LTCSLNDSATEV50, 36KILLTCS42 and 22AAGTVFTTVEDL33 were determined to be the epitopes of HAb18, 3B3 and 1B3, respectively, which were further proved by a dot‐blot analysis with synthesized peptides and bioinformatics epitope prediction. The binding regions of MoAb 5A5 and 4D2 were located at residues E120–R203. Then we constructed and expressed full‐length HAb18G/CD147 and truncated HAb18G/CD147 without residues A22–V50 in COS‐7 cells. Gelatin zymography and Boyden chamber assay showed that the COS‐7 cells expressing truncated HAb18G/CD147 failed to induce MMP production and enhance the cells’ invasive potential, compared with the cells expressing full‐length HAb18G/CD147. Taken together with the obviously inhibitory effects of HAb18 on the function of full‐length HAb18G/CD147, these findings suggest that residues 22AAGTVFTTVEDLGSKILLTCSLNDSATEV50 may play a critical role in the functions of HAb18G/CD147 on MMP secretion and tumour invasion. These key residues can be used as potential drug target in cancer therapy.

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NCT01232621.