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Kim C.,Yonsei University | Chon H.J.,Yonsei University | Kang B.,Yonsei University | Kim K.,Yonsei University | And 7 more authors.
BMC Cancer | Year: 2013

Background: Due to improved survival rate, gastric cancer (GC) patients have an increased risk of developing multiple primary cancer (MPC). The purpose of this study is to evaluate the clinicopathological features of MPC and to generate useful tools for the prediction of metachronous MPC following gastrectomy.Methods: 3066 patients who underwent curative resection of GC were reviewed retrospectively, based on the clinical information and the medical record.Results: The 5-year incidence of MPC was 2.5%. Of these, 54.3% had a metachronous MPC, while 45.7% had a synchronous MPC. The most prevalent site of metachronous MPC was the colorectum (26.3%), followed by lung (23.7%) and liver (18.4%). Multivariate logistic regression analysis revealed that old age at the time of GC diagnosis (≥60 years), early stage of GC (stage I and II), and multiplicity of GC at the time of gastrectomy were independent predictive factors for metachronous MPC. GC patients with either metachronous or synchronous MPC showed poorer survival than patients without MPC. In addition, patients with a metachronous MPC showed late survival disadvantage, while patients with a synchronous MPC showed early survival disadvantage. Furthermore, we were able to develop and internally validate a nomogram to predict the metachronous MPC after curative gastrectomy (C-index = 0.72).Conclusion: Patients at high risk of developing metachronous MPC after curative resection of GC were identified. Individual risk of developing metachronous MPC could be predicted by a novel nomogram. Further external validation with independent patient cohorts is required to improve the accuracy of prediction. © 2013 Kim et al.; licensee BioMed Central Ltd. Source


Jung J.-J.,Yonsei Cancer Research Institute | Noh S.,Yonsei Cancer Research Institute | Jeung H.-C.,Yonsei Cancer Research Institute | Jung M.,Yonsei Cancer Research Institute | And 9 more authors.
Cancer Science | Year: 2010

Gastric cancer (GC) is a heterogeneous disease that is not well detected by current tumor markers. Identifying molecular markers that can predict the potential for tumor progression is important for appropriate individualized therapy. Using the Cancer Metastasis Research Center microarray database (17K cDNA microarray), we identified genes that were differentially expressed between 96 cancer and 98 normal gastric tissues using significant analysis of microarrays. From these, we selected genes that were overexpressed more than twofold in tumor tissues that encode secreted proteins. The selected genes were validated with ELISA using the sera of 96 GC patients and 48 healthy donors. Our first round of selection included 6510 genes that were differentially expressed between 96 cancer and 98 normal gastric tissues with a minimal false discovery rate of 0.005%. Out of those genes, we picked 386 that encoded secreted proteins based on the SOURCE database. Of these genes, we focused on 55 that were overexpressed more than twofold in GC compared to normal tissues. With Ingenuity Pathway Analysis, we found 34 genes related to cancer. One in particular, chemokine growth-regulated oncogene 1, CXCL1, has been linked to cancer progression in various cancer types, but not yet to GC. Levels of CXCL1 in serum samples of GC patients were significantly higher compared with healthy donors (. P < 0.05). Within GC patients, CXCL1 serum levels increased according to tumor stage and lymph node metastasis. The CXCL1 gene appears to be a candidate marker for GC progression. © 2010 Japanese Cancer Association. Source


Noh S.,Cancer Metastasis Research Center | Jung J.-J.,Cancer Metastasis Research Center | Jung J.-J.,National Biochip Research Center | Jung M.,Cancer Metastasis Research Center | And 18 more authors.
Hepato-Gastroenterology | Year: 2011

Background/Aims: We evaluated matrix metalloproteinase (MMP)-2 and -9 as novel biomarkers in the body fluid of advanced gastric cancer with peritoneal and pleural metastasis. Methodology: MMPs activity from zymography was quantified with ELISA to determine the cut-off expression levels of MMPs. The expression of MMPs in patient samples were evaluated with ELISA and compared with clinical parameters. Ascitic CEA (aCEA) and pleural CEA (pCEA) were measured by chemiluminescent enzyme immunoassay. Results: MMP-2 and -9 cut-off levels were 8.6ng/mL and 0.14ng/mL, respectively. Ascitic fluid cytology of 93 patients revealed a positivity of 55.9% while for MMP-2 it was 93.3%, for MMP-9 35.2% and for aCEA 86.7%. Combining biomarkers, the positivity increased to 99.1% in patients with MMP-2 and aCEA expression. We found a negative correlation between MMP-2 expression and survival when a new prognostic cut-off of 22.6ng/mL was used. Patients with high MMP-2 expression (≥22.6ng/mL) had a median survival of 45 days and those with low MMP-2 expression (<22.6ng/mL) had a median survival of 69 days (p<0.01). Conclusions: These results suggest that MMPs could be used as diagnostic markers in body fluid and MMP-2 might be a prognostic marker in ascites of advanced gastric patients with disseminated metastasis. © H.G.E. Update Medical Publishing S.A. Source


Lee W.S.,Cancer Metastasis Research Center | Lee W.S.,Yonsei University | Jung J.J.,Cancer Metastasis Research Center | Jung J.J.,Yonsei University | And 15 more authors.
Hepato-Gastroenterology | Year: 2012

Background/Aims: Epigenetic regulations play a role in the development and progression of cancer. Therefore, discovering novel epigenetically regulated genes could provide useful information in understanding cancer. Lamin A/C is an intermediate filament protein whose expression is reported to be suppressed in tissues of gastro-intestinal malignancies. We examined expression of lamin A/C in gastric and colorectal cancer cell lines and its association with DNA methylation. Methodology: The methylation status of CpG island in 19 gastric, 5 colorectal cancer cells and 1 normal colon cell line were examined with methylation-specific PCR using paired methylated and unmethylated primers. The level of mRNA expression of lamin A/C was detected using RT-PCR. Results: Eighteen gastric cancer cell lines showed 95% unmethylation of lamin A/C and 1 cell line showed partial methylation. In colorectal cancer, only 1 out of 5 cancer cell lines (20%) was partially methylated and the remaining cell lines, including 1 normal colon cell line was unmethylated. With RT-PCR, all cell lines demonstrated mRNA expression of lamin A/C regardless of methylation status. Conclusions: We observed that the expression of lamin A/C was not suppressed in gastrointestinal cancer cell lines different from hematologic malignant cells and it is not regulated through DNA methylation. © H.G.E. Update Medical Publishing S.A. Source


Kim J.H.,Yonsei Cancer Research Institute | Kim J.H.,Cancer Metastasis Research Center | Kim J.H.,Yonsei University | Kim H.S.,Yonsei Cancer Research Institute | And 17 more authors.
Annals of Oncology | Year: 2012

Background: Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. Patients and methods: The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. Results: Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59-1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. Conclusions: A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

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