OBJECTIVE: To investigate the differentially expressed genes between gastric cancer and normal gastric mucosa by bioinformatics analysis, identify the important gene participating in the occurrence and progression of gastric cancer, and predict the functions of these genes. METHODS: The gene expression microarray data GSE100935 (including 18 gastric cancer samples and normal gastric mucosal tissues) downloaded from the GEO expression profile database were analyzed using Morpheus to obtain the differentially expressed genes in gastric cancer, and a cluster analysis heat map was constructed. The online database UALCAN was used to obtain the expression levels of these differentially expressed genes in gastric cancer and normal gastric mucosa. The prognostic value of the differentially expressed genes in gastric cancer was evaluated with Kaplan-Meier survival analysis. GO functional enrichment analysis was performed using Fun-Rich software, and the STRING database was exploited to establish a PPI network for the differentially expressed genes. RESULTS: A total of 45119 differentially expressed genes were identified from GSE100935 microarray data. Analysis with UALCAN showed an obvious high expression of EXD3 gene in gastric cancer, and survival analysis suggested that a high expression level of EXD3 was associated with a poorer prognosis of the patients with gastric cancer. GO functional enrichment analysis found that the differentially expressed genes in gastric cancer were involved mainly in the regulation of nucleotide metabolism and the activity of transcription factors in the cancer cells. CONCLUSIONS EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients.
Computational Biology ; Databases, Genetic ; Exonucleases ; genetics ; Gastric Mucosa ; chemistry ; enzymology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins ; genetics ; Prognosis ; Stomach Neoplasms ; enzymology ; genetics ; mortality

The fundamental event of cancer invasion and metastasis is the complicated interaction of cancer cells with host cells, in which event, a number of proteases and their inhibitors are involved. Matrix metalloproteinases are the potent proteases in degrading the basement membrane and extra cellular matrix and are inhibited by specific endogeneous inhibitors, tissue inhibitors of metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2 was investigated by Northern blot analysis in specimens taken from 27 patients with primary gastric adenocarcinoma; 25 samples from the primary site, six from the metastatic lymph nodes and two from the peritoneal fluids. The expression for TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP-2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared with the those of primary cancer tissues, while one (50%) specimen overexpressed TIMP-2. Immunohistochemical staining was done to investigate the localization of TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was clearly detected in the cytoplasm of the stromal cells. These results suggest that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by stromal cells, may play an important role in inhibiting the proteolytic activity of matrix metalloproteinases originated from cancer cells, in gastric cancer.
Adenocarcinoma/*enzymology ; Blotting, Northern ; Glycoproteins/*biosynthesis/genetics ; Human ; Proteins/*biosynthesis/genetics ; RNA, Messenger/biosynthesis ; Stomach Neoplasms/*enzymology ; Support, Non-U.S. Gov't ; Tissue Inhibitor of Metalloproteinases ; Tissue Inhibitor-of Metalloproteinase-2

The fundamental event of cancer invasion and metastasis is the complicated interaction of cancer cells with host cells, in which event, a number of proteases and their inhibitors are involved. Matrix metalloproteinases are the potent proteases in degrading the basement membrane and extra cellular matrix and are inhibited by specific endogeneous inhibitors, tissue inhibitors of metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2 was investigated by Northern blot analysis in specimens taken from 27 patients with primary gastric adenocarcinoma; 25 samples from the primary site, six from the metastatic lymph nodes and two from the peritoneal fluids. The expression for TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP-2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared with the those of primary cancer tissues, while one (50%) specimen overexpressed TIMP-2. Immunohistochemical staining was done to investigate the localization of TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was clearly detected in the cytoplasm of the stromal cells. These results suggest that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by stromal cells, may play an important role in inhibiting the proteolytic activity of matrix metalloproteinases originated from cancer cells, in gastric cancer.
Adenocarcinoma/*enzymology ; Blotting, Northern ; Glycoproteins/*biosynthesis/genetics ; Human ; Proteins/*biosynthesis/genetics ; RNA, Messenger/biosynthesis ; Stomach Neoplasms/*enzymology ; Support, Non-U.S. Gov't ; Tissue Inhibitor of Metalloproteinases ; Tissue Inhibitor-of Metalloproteinase-2

OBJECTIVETo investigate the association of AKR1B10 expression in gastric cancer tissues with clinicopathologic features and prognosis of gastric cancer patients.

METHODSReal-time polymerase chain reaction (RT-PCR) was conducted to detect AKR1B10 mRNA expression in gastric cancer and adjacent gastric mucosa tissues (n=36). AKR1B10 protein expression was measured by immunohistochemistry in primary gastric cancer tissues (n=100) and non-tumorous gastric mucosa tissues (n=70).

RESULTSRT-PCR results confirmed that AKR1B10 was significantly down-regulated in gastric cancer tissues compared with that in paired adjacent mucosa [8.3% (3/36) vs. 91.7% (33/36), P=0.000]. Immunohistochemistry revealed that the percentage of AKR1B10 positive specimens in gastric carcinoma was lower than that in normal specimens [33.0% (33/100) vs. 92.9% (65/70), P=0.000]. The frequencies of positive AKR1B10 in patients was significantly correlated with tumor size (P=0.000), invasive depth (P=0.004), lymph node metastasis (P=0.028), distant metastasis (P=0.031) and TNM stages (P=0.000). The 5-year survival rate of positive AKR1B10 group was significantly higher as compared to negative group (60.6% vs. 32.8%, P<0.01).

CONCLUSIONThe down-regulation of AKR1B10 expression in gastric cancer may be associated with the progress of gastric cancer is suggestive of poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Aldehyde Reductase ; genetics ; metabolism ; Female ; Gastric Mucosa ; enzymology ; pathology ; Humans ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; Stomach Neoplasms ; diagnosis ; enzymology ; pathology

PURPOSE: Gastric carcinoma tissues release high level of prostaglandin E2 (PGE2) when compared to non-neoplastic mucosa, and cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in prostaglandin (PG) biosynthesis, is often overexpressed in gastric carcinomas and during gastric carcinogenesis. However, little is known about the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for the biological inactivation of PG, in gastric carcinomas. MATERIALS AND METHODS: We investigated the expression of 15-PGDH in 28 cases of advanced gastric carcinomas by Western blot analysis and also the relation between its expression and the gene promoter methylation. RESULTS: 15-PGDH expression was significantly decreased in gastric carcinomas compared to corresponding non-neoplastic tissues and inversely correlated with the expression of proliferating cell nuclear antigen in gastric carcinomas. However, there was no correlation between 15-PGDH expression and pathological findings such as nodal metastasis and vascular invasion. Promoter hypermethylation of 15-PGDH gene was not detected in carcinomas, with only a negligible expression of the enzyme. CONCLUSION: Our results suggested that 15-PGDH has tumor suppressor activity in gastric carcinomas.
Aged ; Base Sequence ; DNA Methylation ; DNA Primers/genetics ; DNA, Neoplasm/genetics ; Female ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics/*metabolism ; Male ; Middle Aged ; Promoter Regions, Genetic ; Stomach Neoplasms/*enzymology/genetics

Humans ; Kisspeptins ; Lymphatic Metastasis ; genetics ; Matrix Metalloproteinase 9 ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; enzymology ; metabolism ; pathology ; Tumor Suppressor Proteins ; genetics

Animals ; Carcinoma, Squamous Cell ; genetics ; Colorectal Neoplasms ; genetics ; metabolism ; Enzyme Activation ; Esophageal Neoplasms ; genetics ; Genome-Wide Association Study ; Head and Neck Neoplasms ; genetics ; Humans ; Neoplasms ; chemically induced ; enzymology ; genetics ; Phosphoinositide Phospholipase C ; chemistry ; genetics ; metabolism ; physiology ; Signal Transduction ; Skin Neoplasms ; chemically induced ; enzymology ; Stomach Neoplasms ; genetics ; Urinary Bladder Neoplasms ; metabolism ; pathology ; ras Proteins ; metabolism

OBJECTIVETo examine the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in gastric carcinoma, and investigate its clinical significance, at the same time analyze the correlation between MT1-MMP and RECK expression.

METHODSMT1-MMP and RECK expression in surgically resected tissue samples of gastric carcinoma was examined by immunohistochemical method (two-step method) , and its correlation with clinicopathological factors was analyzed.

RESULTSAmong the 44 gastric carcinoma samples, 37 (84.1%) were stained positive for MT1-MMP, and 31 (70.5%) for RECK. The expression of MT1-MMP was much higher in poorly differentiated gastric carcinoma samples than moderately and well-differentiated samples (P = 0.015). The expression level of MT1-MMP was associated with invasive depth of tumor cells (P = 0.007), but no difference between sex and lymph node metastasis. On the contrary, the well-differentiated samples showed higher expression of RECK than poorly and moderately differentiated gastric carcinoma samples (P = 0.006). The expression level of RECK did not correlate with sex, lymph node metastasis and invasive depth of tumor cells. RECK expression showed no relation to MT1-MMP expression in the gastric carcinoma.

CONCLUSIONOverexpression of MT1-MMP in gastric carcinoma may play an important role during tumor differentiation and metastasis, the RECK protein may have positive effects on the tumor differentiation.

Adult ; Aged ; Aged, 80 and over ; Carcinoma ; enzymology ; genetics ; metabolism ; pathology ; Female ; GPI-Linked Proteins ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 14 ; genetics ; metabolism ; Middle Aged ; Stomach Neoplasms ; enzymology ; genetics ; metabolism ; pathology

OBJECTIVETo explore the relationship between heparanase mRNA expression and clinicopathological parameters in human gastric cancer.

METHODSRT-PCR was used to detect the expression of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues.

RESULTSHeparanase mRNA was expressed in 29 of the 43 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than that in adjacent normal gastric tissues (P = 0.013). The expression level was higher in late-stage tumors (stage III and IV) than in early-stage tumors (stage I and II) (P = 0.001), in tumors with invasion to serosa than those without serosal invasion (P = 0.009), in tumors with lymph node metastasis than those without lymph node metastasis (P = 0.018), and in large-sized tumors than in small-sized ones (P = 0.009). The expression was not correlated with patients' age, sex, tumor location, histologic types, differentiation, peritoneal dissemination and liver metastasis (P > 0.05).

CONCLUSIONHeparanase might play an important role in the development of invasion and metastasis of gastric cancer.

Adenocarcinoma ; enzymology ; pathology ; Adult ; Aged ; Aged, 80 and over ; Female ; Glucuronidase ; biosynthesis ; genetics ; Humans ; Liver Neoplasms ; metabolism ; secondary ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; enzymology ; pathology

OBJECTIVETo study the correlation between expression of urokinase-type plasminogen activator (uPA) and capability of tumor cell seeding to the peritoneal membrane by different gastric cancer lines.

METHODSExpression of uPA in 4 human gastric cancer cell lines was examined by semi-quantitative RT-PCR, ELISA and Western blot. uPA activity was determined by an assay kit. After ip inoculation of cancer cells to nude mice, tumors on peritoneal membrane was grossly examined for tumor cell seedings.

RESULTSSGC7901 was the highest in uPA expression among human gastric cancer cell lines AGS, SGC7901, MKN45, and MKN28. MKN45 had the strongest uPA activity, while AGS was lowest in both uPA expression and activity. Peritoneal seeding tumors of various sizes were observed in mice inoculated with SGC7901 and MKN45 cells. In addition to peritoneal seedings, bloody ascites was present in mice inoculated with MKN28. The MKN45-inoculated mice took the least time to develop tumors and had the shortest surviving period. No peritoneal seeding was seen in mice inoculated with AGS cells.

CONCLUSIONThree of 4 human gastric cancer cell lines studied express uPA mRNA and activity, which correlate with their peritoneal seeding potentials.

Adenocarcinoma ; enzymology ; secondary ; Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Seeding ; Peritoneal Neoplasms ; secondary ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; enzymology ; pathology ; Urokinase-Type Plasminogen Activator ; biosynthesis ; genetics