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

To elucidate the clinical significance of phenotypic alterations of Lewis antigen in gastric cancer patients, we investigated Lewis antigens by analyzing the genotypes of the Le and Se genes and by comparing the results obtained with the phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells. One hundred and twenty gastric cancer patients were examined and compared with respect to Lewis blood phenotype and genotype. The expression of Lea, Leb, sialylated Lea, and sialylated Lex antigens was immunohistochemically examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous tissue. We also analyzed the significance of Lewis antigen expression by analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%, respectively. The Le and le allele gene frequencies calculated from genotyping in gastric cancer patients were 0.623 and 0.377, respectively. The frequency for Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than in normal healthy Koreans. However, no difference in the Lewis gene frequency was found between these gastric cancer patients and healthy persons. The phenotype of Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the most prevalent form in tumor tissue was Le(a-b-). Sialyl-Lea and sialyl-Lex antigens were hardly detectable in uninvolved gastric mucosa, whereas the two antigens were expressed highly in intestinal metaplastic mucosa and tumor cells. In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in gastric cancer patients is not a result of genetic influences, but rather a result of sialylation in tissue. We also confirm that poor prognosis is associated with dimeric sialyl-Lex and vascular spread.
Adult ; Aged ; Alleles ; Erythrocytes/*chemistry ; Female ; Fucosyltransferases/*analysis/genetics ; Gangliosides/analysis ; Genotype ; Human ; Immunohistochemistry ; Male ; Metaplasia ; Middle Age ; Oligosaccharides/analysis ; Phenotype ; Stomach Neoplasms/*blood/genetics/mortality

OBJECTIVETo investigate the therapeutic principles and prognosis of synchronous primary colorectal carcinomas (SCC).

METHODSThe data of 66 SCC patients surgically treated from 1984 to 2003 were retrospectively reviewed.

RESULTSThe synchronous primary colorectal carcinomas were diagnosed and resected simultaneously in 65 patients except one that was misdiagnosed. Thirty patients underwent combined resection, 35 patients segmental resection. Sixty-two patients received radical resection, while three patients had palliative resection due to hepatic metastasis. The overall postoperative 3-, 5-, 10-year survival rates were 70.3%, 60.0%, 40.6%, respectively. In the patients who had simultaneous radical resection, the 3-, 5-, 10-year survival rates were 76.0%, 65.9%, 46.4% respectively.

CONCLUSIONThe extent of resection should be individually determined by the lesion location, extent and distance between the lesions, as well as the patient's general condition. More extensive bowel resection, such as total or subtotal colectomy are suggested for those patients with hereditary nonpolyposis colorectal carcinoma syndrome in order to reduce or avoid the risk of metachronous colorectal carcinoma. The postoperative survival in patients with synchronous primary colorectal carcinoma is similar to those with solitary lesion.

Adult ; Aged ; Colorectal Neoplasms ; mortality ; pathology ; surgery ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; genetics ; surgery ; Ovarian Neoplasms ; surgery ; Prognosis ; Stomach Neoplasms ; surgery ; Survival Rate

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Colorectal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Esophageal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Gastrointestinal Tract ; metabolism ; pathology ; Gene Expression ; Humans ; Neoadjuvant Therapy ; methods ; Neoplasm Grading ; Neoplasms, Vascular Tissue ; diagnosis ; drug therapy ; mortality ; secondary ; Prognosis ; SOXB1 Transcription Factors ; genetics ; metabolism ; Stomach Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Survival Analysis

BACKGROUND: The aim of this study was to determine the prognostic significance of the expression of p53 and retinoblastoma (Rb) gene products in cases of curatively resected gastric adenocarcinoma, by immunohistochemical analysis. METHODS: Between January 1996 and December 2001, 736 curatively resected gastric cancer patients underwent immunohistochemical staining for p53 or Rb proteins (pRb), and we retrospectively analyzed the correlation of our results with the clinical outcomes of these cases. RESULTS: High levels of expression of p53 (> 25% p53-positive cells) and Rb (> 50% Rb-positive cells) proteins were detected in 40.1% and 43.7% of cases, respectively. Tubular type was found to frequently exhibit higher levels of p53 expression (high expression in 44.2%) than signet ring cell type (high expression in 26.0%) (p=0.042). The incidence of vascular invasion was lower in the high pRb expressors (43.2%) than in the pRb low expressors (56.8%), but this was not a statistically significant discrepancy (p=0.063). Preoperative CEA levels were found to be low in high pRb expressors: initial CEA level in the high pRb expressors was 2.31 +/- 3.30 ng/mL, and was 5.18 +/- 24.80 ng/mL in the low pRb expressors (p=0.033). Tumor depth and node metastasis were both independent of the levels of expression of p53 and Rb proteins. The seven-year overall survival rate and relapse-free survival rates of patients were 87.2% and 75.7%, respectively. Multivariate Cox regression analysis indicated that tumor stage, tumor size, patient age and pRb expression were the significant prognostic factors with regard to overall survival, and tumor stage and age were both significant factors with regard to relapse-free survival. CONCLUSION: Immunohistochemical staining of retinoblastoma gene products was an independent prognostic factor for the prediction of overall survival in curatively resected gastric cancer patients.
Adenocarcinoma/*genetics/metabolism/mortality ; Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Protein p53/*metabolism ; Retinoblastoma Protein/*metabolism ; Retrospective Studies ; Stomach Neoplasms/*genetics/metabolism/mortality

OBJECTIVETo investigate the expression of osteopontin (OPN) splice variant mRNA, including the three isoforms OPN-A, OPN-B, and OPN-C, to explore its correlation with clinicopathologic features in gastric cancer, and to elucidate their role in tumor invasion and distant metastasis of gastric cancer.

METHODSThe expression of OPN-A, OPN-B and OPN-C mRNA were detected by real-time reverse transcriptase-polymerase chain reaction in 66 gastric cancer tissues. The relationship between the expression of OPN-A, OPN-B and OPN-C mRNA and clinicopathologic features of gastric cancer was analyzed.

RESULTSThe expression of OPN-C mRNA in the gastric cancer tissue was 3.21-fold higher than that in peritumoral mucosal tissue, showing a significant difference between them (P < 0.001). OPN-C mRNA expression was correlated with the depth of tumor invasion, tumor diameter, lymph node meatastasis, distant meatastasis and had no correlation with differentiation grades. The low expression of OPN-C mRNA was correlated with long survival benefit (P = 0.03). The expression of OPN-A and OPN-B mRNA had no significant relationship with clinicopathologic features of gastric cancer.

CONCLUSIONSOne of the isoform of osteopontin (OPN) OPN-C mRNA is overexpressed in gastric cancer. The overexpression of OPN-C mRNA may reflect the progression and is associated with the prognosis of gastric cancer. OPN-C mRNA may have value as a prognostic biomarker in gastric cancer. However, the expression of OPN-A and OPN-B are not correlated with the progression and metastasis of gastric cancer.

Disease Progression ; Gastric Mucosa ; metabolism ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; Osteopontin ; genetics ; Prognosis ; Protein Isoforms ; genetics ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Stomach Neoplasms ; genetics ; mortality ; pathology

BACKGROUND/AIMS: Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU) and has a polymorphic 28 bp tandem repeated sequence. TS enhancer region (TSER) polymorphism has been associated with the efficacy of 5-FU-based chemotherapy in colon cancer. Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to methyl donor for DNA methylation. The aim of this study was to determine the clinical value of TSER and MTHFR polymorphism in gastric cancer. METHODS: From October, 1995 to February, 2002, 40 gastric cancer patients underwent operation and 25 patients among those patients have received postoperative 5-FU-based chemotherapy (5-FU (+) group). Peripherial blood were sampled for TSER and MTHFR genotype analysis by PCR amplification of genomic DNA. The survival of patients according to TSER and MTHFR polymorphism were compared. RESULTS: We observed a longer survival in stage II than stage III of the patients (p=0.0037). However, the TSER and MTHFR C677T polymorphisms were not associated with better survival of gastric cancer patients as well as combined TSER and MTHFR genotypes with 5-FU chemotherapy. CONCLUSIONS: The TSER and MTHFR genotypes are not effective markers for tumor sensitivity to 5-FU-based chemotherapy in Korean gastric cancer patients after curative resection. These results may suggest further large-scale study about TSER and MTHFR polymorphism for the prediction of efficacy of 5-FU-based chemotherapy in gastric cancer in Korea.
Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Drug Screening Assays, Antitumor ; Female ; Fluorouracil/*therapeutic use ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; *Polymorphism, Genetic ; Stomach Neoplasms/*drug therapy/genetics/mortality ; Survival Rate ; Thymidylate Synthase/*genetics

OBJECTIVETo investigate mRNA expression of syndecan-1 and heparanase in gastric carcinoma, and their correlation with the growth-pattern, invasion, metastasis and prognosis of gastric carcinoma.

METHODSIn situ hybridization technique was used to examine mRNA expression of syndecan-1 and heparanase in 118 specimens of gastric carcinoma.

RESULTSThe positive rates of syndecan-1 mRNA and heparanase mRNA were 42.4% and 55.9%, respectively. The expression of syndecan-1 mRNA and heparanase mRNA were related to tumor invasion depth (chi(2) = 32.95, P = 0.001; chi(2) = 23.19, P = 0.001), vessel invasion (chi(2) = 46.22, P = 0.001; chi(2) = 33.78, P = 0.001), lymph node (chi(2) = 28.62, P = 0.001; chi(2) = 25.43, P = 0.001) and distant metastasis (chi(2) = 63.30, P = 0.001; chi(2) = 65.76, P = 0.001), and syndecan-1 mRNA positive expression was related to tumor size (chi(2) = 6.25, P = 0.012). There was a negative relationship between Syndecan-1 mRNA and heparanase mRNA expression (r = -0.844, P = 0.001). The mean survival time of cases with low expression of syndecan-1 mRNA was significantly shorter than that of cases with high expression (r = 36.48, P = 0.001), and meanwhile, the mean survival time of heparanase mRNA positive cases was significantly shorter than that of cases with negative expression (r = 34.41, P = 0.001).

CONCLUSIONSThe mRNA expression of syndecan-1 and heparanase can predict the invasion and metastasis of gastric carcinoma, and can be used as markers of prognosis of gastric carcinoma.

Adult ; Aged ; Female ; Follow-Up Studies ; Glucuronidase ; genetics ; metabolism ; Humans ; In Situ Hybridization ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Stomach Neoplasms ; metabolism ; mortality ; pathology ; Survival Rate ; Syndecans ; genetics ; metabolism

Although N-myc downstream regulated gene 2 (NDRG2) has been known to be a tumor suppressor gene, the function of this gene has not been elucidated. In the present study, we investigated the expression and function of NDRG2 in human gastric cancer. Among seven gastric cancer and two non-cancer cell lines, only two gastric cancer cell lines, SNU-16 and SNU-620, expressed NDRG2, which was detected in the cytoplasm. Interestingly, NDRG2 was highly expressed in normal gastric tissues, but gastric cancer patients were divided into NDRG2-positive and -negative groups. The survival rate of NDRG2-negative patients was lower than that of NDRG2-positive patients. We confirmed that the loss of NDRG2 expression was a significant and independent prognostic indicator in gastric carcinomas by multivariate analysis. To investigate the role of NDRG2 in gastric cancer cells, we generated a NDRG2-silenced gastric cancer cell line, which stably expresses NDRG2 siRNA. NDRG2-silenced SNU-620 cells exhibited slightly increased proliferation and cisplatin resistance. In addition, inhibition of NDRG2 decreased Fas expression and Fas-mediated cell death. Taken together, these data suggest that inactivation of NDRG2 may elicit resistance against anticancer drug and Fas-mediated cell death. Furthermore, case studies of gastric cancer patients indicate that NDRG2 expression may be involved in tumor progression and overall survival of the patients.
Apoptosis/*physiology ; Cell Line, Tumor ; Down-Regulation ; Fas Ligand Protein/*physiology ; Gene Expression Regulation, Neoplastic ; Humans ; Stomach Neoplasms/metabolism/*mortality/pathology ; Tumor Markers, Biological/*metabolism ; Tumor Suppressor Proteins/biosynthesis/genetics/immunology/*metabolism

BACKGROUND/AIMS: The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated. METHODS: The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses. RESULTS: The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes. CONCLUSIONS: MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry/*statistics & numerical data ; Kaplan-Meier Estimate ; Male ; *Microsatellite Instability ; Middle Aged ; Phenotype ; Polymerase Chain Reaction ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Sensitivity and Specificity ; Sex Factors ; Stomach Neoplasms/*genetics/mortality