Gastric cancer is one of the most common cancers worldwide. The purpose of this study was to find out potential markers for gastric cancer. Tumor and normal tissues from 152 gastric cancer cases were analyzed by two-dimensional gel electrophoresis (2-DE). The images of silver stained gels were analyzed and statistical analysis of spot intensities revealed that spot 4262 showed higher expression (5.7-fold increase) in cancer tissues than in normal tissues (P <0.001). It was identified by peptide mass fingerprinting as nicotinamide N-methyltransferase (NNMT). A monoclonal antibody with a detection limit down to 10 ng was produced against NNMT in mouse. Using the prepared monoclonal antibody, western blot analysis of NNMT was performed for gastric tissues from 15 gastric cancer patients and two gastric ulcer patients. The results corroborated those of 2-DE experiments. A single spot was detected in gastric ulcer tissues while four to five spots were detected in gastric cancer tissues. In cancer tissues, two additional spots of acidic and basic form were mainly detected on 2-DE gels. This suggests that NNMT receives a post-translational modification in cancer-specific manner.
MAD2 is localized to kinetochores of unaligned chromosomes, where it inactivates the anaphase-promoting complex/cyclosome, thus contributing to the production of a diffusible anaphase inhibitory signal. Disruption of MAD2 expression leads to defects in the mitotic checkpoint, chromosome missegregation, and tumorigenesis. However, the mechanism by which deregulation and/or abnormality of hsMAD2 expression remains to be elucidated. Here, we clone and analyze a ϳ0.5 kb fragment upstream of hsMAD2 and show that this fragment acts as a strong promoter. Transcriptional dysfunction of hsMAD2 is frequently observed in hepatocellular carcinoma cells, and down-regulation of hsMAD2 protein expression is correlated with transcriptional silencing of the hsMAD2 promoter by hypermethylation. These results imply a relationship between transcriptional abnormality of this mitotic checkpoint gene and mitotic abnormality in human cancers.
F-actin capping protein α1 subunit (CAPZA1) was previously identified in a proteomic analysis of human gastric cancer clinical specimens and selected for further study. The association between CAPZA1 overexpression, detected by immunohistochemistry, and clinicopathological features including survival were evaluated. In vitro gain-of-function and loss-of-function approaches were utilized to assess the function of CPAZA1 in malignancy. Univariate analysis revealed that poorly differentiated disease, according to the World Health Organization (WHO) classification, advanced T stage, positive lymph nodes, high TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1 underexpression were significantly associated with cancer-related death (p<0.05); however, only high TNM stage remained significantly associated by multivariate analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated histology, smaller tumor size, lower T stage, absence of lymph node metastasis, lower TNM stage, lower recurrence rate and longer survival time, compared to CAPZA1 underexpression. In vitro, forced expression of CAPZA1 caused a significant decrease in gastric cancer cell migration and invasion, whereas CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion.
Decreased expression of ANXA3 in papillary thyroid cancer supports the idea that ANXA3 may be an effective marker of microcarcinoma, and a negative predictor of papillary thyroid cancer progression.
Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.
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