Levels In Gastric Cancer Research Articles

Serum angiopoietin-like protein 2 as a novel biomarker of diagnosis and prognosis in gastric cancer.

9 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and is known to act as a causative mediator of chronic inflammation and inflammatory carcinogenesis. Recently, we demonstrated that ANGPTL2 overexpresses in gastric cancer (GC) compared to normal gastric mucosa and high ANGPTL2 is associated with poor prognosis. Therefore, if tumor-derived ANGPTL2 over-secretes systemically, focusing ANGPTL2 in blood is logical to evaluate its ability as a biomarker. Accordingly, we quantified serum ANGPTL2 level and assessed its clinical significance in GC patients. Methods: We screened serum ANGPTL2 levels from 32 GC and 24 normal controls (NC) by ELISA (cohort 1). Next, we validated 194 serum samples from GC and 48 NC (cohort 2). Finally, we examined ANGPL2 expression in matched GC tissues of cohort 2 (n=194) by immunohistochemistry (IHC). The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: In cohort 1,serum ANGPTL2 levels in GC were significantly higher than that in NC (p<0.05). Serum ANGPTL2 differentiated GC from NC with high accuracy (AUC=0.814). Analysis of cohort 2 also indicated that serum ANGPTL2 levels in GC were significantly higher compared to NC (p<0.0001), and increased according to UICC stage progression. In addition, serum ANGPTL2 had a promising AUC (0.831) with high sensitivity (73.0%) and specificity(82.2%) to distinguish GC from NC. High serum ANGPTL2 was significantly associated with lymphatic invasion (p=0.03), vessel invasion (p=0.02), distant metastases (p=0.0002), early recurrence (p=0.004) and poor survival (p=0.01), consequently emerged as an independent predicting recurrence marker (HR=5.06, p=0.0004) and prognostic marker (HR=3.6, p=0.01) in GC. Of interest, ANGPTL2 levels in serum from GC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 at the invasive margin of matched GC tissues (r= 0.16, p=0.02). Conclusions: Serum ANGPTL2 levels, which might be secreted from primary or metastatic site into blood stream, have extremely strong potential as a novel biomarker for diagnosis, predicting recurrence and poor prognosis in GC patients.

MicroRNA‐143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer

Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. In the present study, we identified several miRNAs that are expressed at higher levels in scirrhous type GC than in non-scirrhous type GC by miRNA microarray analysis. Among these, microRNA-143 (miR-143) expression was higher in scirrhous type GC than in non-scirrhous types of GC. In situ hybridization and quantitative RT-PCR analysis showed that miR-143 is expressed by stromal fibroblasts but not by cancer cells. In stromal cells, miR-143 enhanced collagen type III expression in normal gastric fibroblasts and cancer-associated fibroblasts through activation of transforming growth factor-β)/SMAD signaling. Furthermore, high miR-143 expression in GC was associated with worse cancer-specific mortality (P = 0.0141). Multivariate analysis revealed that miR-143 was an independent prognostic factor. Treatment of GC cell lines with 5-aza-2′-deoxycytidine restored the expression of miR-143, and precursor miR-143 caused the inhibition of cancer cell invasion. These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and that miR-143 expression serves as a prognostic marker of GC.

Expression of SM22α in Gastric Cancer

Objective To investigate the expression levels of cytoskeleton-related protein SM22α in gastric cancer or adjacent normal gastric mucosa tissues. Methods RT-PCR and Western blotting were performed to detect SM22α mRNA and protein levels in gastric cancer tissues and adjacent normal gastric mucosa tissues.RT-PCR and zymography were used to detect MMP9 mRNA level and activity in gastric cancer tissues and adjacent normal gastric mucosa tissues,respectively. Results Both SM22α mRNA and protein levels in gastric cancer were significantly lower than that in adjacent normal gastric mucosa tissues(P0.05). The expression and activity of MMP9 in gastric cancer cases were significant higher than that in adjacent normal gastric mucosa tissues(P0.05). A negative correlation was found between SM22α protein level and MMP9activity in gastric cancer tissues. Conclusion SM22α is downregulated in gastric cancer. SM22α may probably inhibit metastasis through negative regulation of MMP9 expression in gastric cancer.

Pepsinogen I and II expressions in situ and their correlations with serum pesignogen levels in gastric cancer and its precancerous disease

BackgroundSerum pepsinogen (PG) I/II ratio has been widely used as “serological biopsy” for the screening of gastric cancer (GC) and atrophic gastritis (GA). However, study concerning in situ expression of PGs is currently insufficient, particularly for their relationship with serum PGs levels. This study was designed to investigate in situ expression of PGI and PGII in subjects with normal mucosa (NOR), superficial gastritis (GS), GA and GC, and to evaluate the correlations between PGs expressions in situ and in serum.Methods185 subjects were enrolled for the study, including 30 NOR, 70 GS, 54 GA and 31 GC. PGI and PGII expressions in situ and in serum were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. H. pylori immunoglobulin (Ig) G was also determined by ELISA.ResultsIn situ expressions of PGI, PGII and PGI/II ratio consistently decreased in sequence of NOR/GS- > GA- > GC. The expressions of PGI, PGII and PGI/II ratio in situ were statistically higher in youngers than in olders (P < 0.05). In the NOR subjects, PGI staining was statistically higher in males than that in females (p = 0.02). For the correlations between in situ and serum expressions of PGI, PGII and PGI/II ratio, a borderline correlation in the total study sample (r = 0.131, P = 0.076) and a statistical correlation in GA cases (r = 0.307, P = 0.027) were observed for the PGI/II ratio. The PGI expression correlated well with that of PGII in situ and in serum.ConclusionsThe in situ levels of PGI, PGII and PGI/II ratio sharply decreased in the GA and GC cases. The youngers exhibited higher levels of PGI, PGII and PGI/II ratios than the olders. The in situ PGI/II ratio rather than PGI and PGII alone showed certain correlation with that in serum, and the PGI expression correlated well with PGII expression. Further studies with large-scale samples are still required to validate our findings.

Prognostic Role of Human Epidermal Growth Factor Receptor in Gastric Cancer: A Systematic Review and Meta-analysis

Human epidermal growth factor receptor (EGFR) and HER2 (ErbB2) both belong to EGFR family, which are overexpressed in a significant proportion of cases of gastric cancer (GC). Various studies have evaluated the prognostic value of EGFR or HER level in GC. However, the overall test performance remains unclear. We undertook this study to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of EGFR or HER2 as a predictor of survival time in patients with GC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle-Ottawa Tool. Data were collected comparing overall survival (OS) in patients with high and low EGFR or HER2 level. Studies were pooled and summary hazard ratios were calculated. Studies were listed twice if they provided overall survival data for both EGFR and HER2. Eight studies (seven for EGFR and eight for HER2) were included. Two distinct groups were pooled for analysis and revealed that high EGFR, HER2 levels predicted poor overall (HR = 1.66, 95% CI: 1.35-2.02) and (HR = 1.43, 95% CI: 1.09-1.88) survival. No publication bias was found. This meta-analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients.

Up-regulation of Ago2 expression in gastric carcinoma

Argonaute (Ago) proteins have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and thus play key roles in carcinogenesis. Nevertheless, little is known about the specific role of Ago2 in gastric cancer (GC). Thus, we aimed to study the expression of Ago2 in 363 primary GC, 8 corresponding lymph node metastases and 10 non-neoplastic surrounding gastric epithelium tissues by immunohistochemical analyses and tissue microarray. The expression of Ago2 was also correlated with clinicopathological characteristics and HER-2 status. Ago2 expression levels in primary GC and corresponding lymph node metastases were significantly higher compared with healthy controls (P < 0.05). But, there was no difference of Ago2 between GC and its metastatic lymph node (P > 0.05). Ago2 up-regulation had no correlation with GC patients' age, tumor location, tumor size, gross morphology or tumor infiltration. However, we found that Ago2 was different between HER-2 positive and HER-2 negative groups (P = 0.044), which had been demonstrated to be related to GC prognosis. And there was a great correlation between Ago2 expression and the tumor differentiation (P = 0.007), lymph node invasion (P = 0.000) and clinical stage (P = 0.006). Interestingly, Ago2 was also correlated to patients' gender (P = 0.004), which may suggest a possible role of hormonal signal in the mechanisms of Ago2. Thus, our results suggested that up-regulation of Ago2 may play an important role in GC carcinogenesis and progression. Further studies on the cellular functions of Ago2 need to address these issues.

Differences in the survival rate between premenopausal and post menopausal women with gastric cancer: U.S. SEER database.

e15092 Background: Gastric cancer is the fourth most common malignancy in the world, The presence of estrogen receptor alpha (ER a) and estrogen receptor beta (ER b) have been reported in cell and tissue level in gastric cancer, but its impact on patients' survival remains unclear. The male predominance of gastric cancer suggests that female sex hormones may have a protective effect against gastric cancer. To understand the clinical impact of the estrogen pathway, we analyzed the national SEER database to compare the outcomes for gastric cancer in premenopausal vs.postmenopausal women. Methods: Data from the national SEER registry between the years of 1985-2009 was analyzed. Women between the ages 31-50 were chosen as representative of the pre-menopausal group (n=1291) and 51-70 year-old women represented the post-menopausal group (n=3089) as defined by the American College of Obstetricians and Gynecologists. To control the effect of age alone as a determinant of outcome, we compared the survival between men were similarly divided into two categories: younger men (n = 2114) aged 31- 50 years and older men (n = 5102) aged 51 - 70 years. Survival rates were analyzed by Kaplan-Meier method and compared by Z-test through SEER*Stat software version 7.0.9. Results: The cardiac gastric cancer site type and diffuse histological subtype had statistical significance difference between premenopausal and postmenopausal groups (49% vs.72%), (44% vs. 692%) respectively. The Kaplan-Meier curve shows the survival rate in premenopausal superior to postmenopausal women in diffuse gastric cancer P=0.01, while no statistically significant difference regarding mixed sub-types P&gt;0.05 and control groups. Conclusions: The results suggest varying estrogen effects between localization and histological subtype of gastric cancer, the presence of estrogen in gastric cancer could have a protective effect against gastric cancer and support clinical strategies need to stimulate the ER pathway or use estrogen for the treatment of gastric cancer, and additional studies are warranted as well as experimental studies that can shed light on the mechanism underlying this potentially protective action.

Su1990 Integrative Identification of EBV-Associated Variations At Genomic, Epigenomic and Transcriptomic Levels in Gastric Cancer

Su1990 Integrative Identification of EBV-Associated Variations At Genomic, Epigenomic and Transcriptomic Levels in Gastric Cancer

Abstract 643: Gene methylation as a novel marker in gastric cancer.

Abstract Introduction: Epigenetics is one of the major cause of cancer. Several studies have shown the relation between gastric cancer and DNA methylation but it lacks coherence to use as a biomarker. Also there is a lot of genes have not reveled correlation between gastric cancer and DNA methylation. Here, we analyze the correlation between DNA methylation and gene expression in gastric cancer to use as a novel biomarker. Method: Gastric cancer and matched normal gastric tissues were obtained who received gastrectomy in Seoul national university. More than 70 % of tumor share tissues were selected for this study. Nine genes (FAM58A, MAL, TMEM220, MMP28, C2orf3, IL-19, RIN2, HOPX, RGS6) expression level were analyzed using 30 pairs of gastric cancer, normal gastric tissues We then selected genes showing distinct difference mRNA expression level between gastric cancer and gastric tissues to analyze DNA methylation level using bisulfite modification. After that we analyze gene expression level and methylation level using 10 gastric cancer cell line(MKN28, AGS, KATOIII, ect..)to compare with gastric cancer tissues Result: Advanced research of this study performed MIRA for analyze DNA methylation level and Real-time pcr to know mRNA expression level using three snap-frozen gastric cancer and matched normal gastric tissue. This study identified that FAM58A, RYR2, SLC9A7, GHSR, HIST1H4E, MAL, TMEM220,C2orf3, MMP28, EPOR etc sixteen genes were hypermethylated in gastric cancer and there were correlation between methylation level and mRNA expression level Also this study found ten hypomethylated genes (STAC, IL19,HYDIN, C1orf162, OR2J2, RIN2,HOPX, RGS6,MOCS1 ect) using three gastric tissue samples. These genes also associated with mRNA expression level comparison between gastric cancer and normal gastric tissues. Among the hypermethylated genes, we analyzed FAM58A, MAL, TMEM220, MMP28, C2orf3 genes MAL(p&amp;lt;0.00004), TMEM220(P&amp;lt;0.0002), MMP28(P&amp;lt;0.00011) mRNA expression level were significantly down-regulated in gastric cancer tissues.. Especially MAL gene is remarkably down-regulated in all 30 samples of gastric cancer tissues. Additionally we analyzed four hypomethylated genes (hand IL-19, RIN2, HOPX, RGS6). RIN2, HOPX, RGS6) but RIN2, HOPX, RGS6 genes mRNA expression level differ in each gastric cancer tissues The other hand IL-19 have shown different mRNA expression level what we expected in advanced study. Except three dramatically up-regulated tissues, almost the others mRNA expression level were down-regulated in 30 gastric cancer tissue samples(p&amp;lt;0.027) Conclusion: Our finding will provide valuable data for development of the useful gastric cancer methylation marker and understanding of correlation between methylation and mRNA expression level in gastric cancer. Furthermore MAL gene case, we expect it could be a gastric cancer marker not only methylation analysis but also mRNA expression level analysis. Citation Format: Boram Choi, Tae-Su Han, Ji-Yeon Lee, Sunmin Lee, Seong-Ho Kong, Hyuk-Jun Lee, Young-Joon Kim, Han-Kwang Yang. Gene methylation as a novel marker in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 643. doi:10.1158/1538-7445.AM2013-643

SERUM PEPSINOGEN I LEVELS IN GASTRIC CANCER

Objective: Identification of serum Pepsinogen I levels in gastric cancer. Materials and Methods: Serum pepsinogen I levels was measured by enzym-linked immunosorbent assay (ELISA) on 32 patients in the gastric cancer group diagnosed by endoscopy and histology and control group of 30 patients with functional dyspepsia on endoscopy Using the cut-off value: PGI ≤ 70 ng/ml for gastric cancer. Results: Median Pepsinogen I levels in gastric cancer group was 41.07 ng / ml (25% quartile: 27.83 ng / ml, 75% quartile: 61.57 ng/ml) was significantly lower in control group: 102.03 ng / ml (25% quartile: 57.63 ng / ml, 75% quartile: 129.32 ng/ml) (p&lt;0.001). The rate of Serum Pepsinogen I (≤ 70 ng/ml) was 78.1% in patients with gastric cancer, was 26.7% in the control group. Serum Pepsinogen I test in cut-off value ≤ 70 ng/ml had a sensitivity of 78.1%, specificity 73.3%, positive predictive value of 75.8% and the predictive value negative of 75.9% (p &lt;0.001). The results of the ROC curve: area under the curve = 0.846,p &lt;0.0001 at the cut-of of Pepsinogen I levels in our study ≤ 50.83 ng/ml with the optimal sensitivity and specificity were 65.6% and 86.7%. Key words: serum Pepsinogen I, gastric cancer

Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features

ObjectiveTo investigate the relationship between the expression of epidermal growth factor receptor (EGFR) in gastric cancer and the clinicopathological features and prognosis. MethodsA total of 78 paraffin specimens of gastric cancer operation were collected. The immunohistochemical method was used to detect the expression of EGFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue. The relationship between the high expression of EGFR and clinicopathological features was analyzed. ResultsEGFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7 % (45/78), while EGFR was not expressed in 20 cases of adjacent normal tissue. The high EGFR expression was positively correlated with the position of gastric cancer, tumor size, cell differentiation, invasive depth, lymph node metastasis and TNM staging, yet having no obvious relation with gender or age. ConclusionsEGFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer, which can provide a theoretical basis for the targeted therapy for gastric cancer with EGFR as the target.

The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer

Gastric cancer is the second leading cause of cancer mortality, but the molecular mechanisms underlying its progression and metastasis remain unclear. CCR7 and Dicer 1 protein expression in 80 gastric adenocarcinomas and 40 peritumoral tissues were measured by immunohistochemical staining. The expression of let-7a miRNA in serum, tumor tissues, and peritumoral tissues was measured by real-time PCR. The role of let-7a in CCR7 protein expression, migration, and invasion of gastric cancer cells was tested in vitro. Dicer 1 protein expression was found to be significantly reduced, whereas CCR7 protein expression was significantly increased in gastric adenocarcinomas compared to peritumoral tissues. The let-7a miRNA levels in the serum and tumor tissues of gastric adenocarcinoma patients were significantly lower than in the serum of healthy controls and peritumoral tissues, respectively. Dicer 1 protein positively correlated with let-7a miRNA level, but negatively correlated with CCR7 protein level in gastric adenocarcinoma. Negative Dicer 1 protein and let-7a miRNA expression and positive CCR7 protein expression significantly correlated with lymph node metastasis, depth of invasion, high clinical TNM stage, and larger tumor size. Let-7a transfection significantly inhibited CCR7 protein expression, migration, and invasion of MNK-45 cells in vitro. High expression of CCR7 protein and low expression of Dicer 1 protein and let-7a miRNA are significantly associated with the metastasis and progression of gastric cancer. High CCR7 protein expression may be caused by the loss of Dicer 1 protein expression and reduced let-7a miRNA level in gastric cancer. The serum let-7a level might be a marker for the diagnosis of gastric cancer.

Diagnostic Significance of Serum Eotaxin-1 Level in Gastric Cancer Patients

Introduction. Gastric cancer is the second cause of cancer-related deaths worldwide. Delayed diagnosis leads to high mortality rates. Eotaxin-1 was originally discovered as an eosinophil-selective chemoattractant and may play a role in a number of chronic inflammatory diseases, cancer, and other gastrointestinal disorders. The aim of this study was to analyse diagnostic and prognostic significance of serum eotaxin-1 (s-eotaxin-1) levels in gastric cancer. Methods. Sixty gastric cancer patients and 69 healthy subjects were included into the study. S-eotaxin-1 levels were compared with clinicopathological features and outcomes in gastric cancer. Results. Serum levels of eotaxin-1 in gastric cancer patients were significantly higher than controls (74.51 ± 16.65 pg/mL versus 16.79 ± 5.52 pg/mL, respectively (P < 0.001)). The s-eotaxin-1 levels did not differ significantly with histopathological grade, tumor-node-metastasis (TNM) stage, tumor localization, lymph node metastases, positive lymph node ratio, size, perineural and perivascular invasion. So there is no relationship found between s-eotaxin-1 level and prognosis. Conclusion. S-eotaxin-1 levels may be used as an easily available biomarker for gastric cancer risk and may alert physicians for early diagnosis. Due to the limited number of patients included in this study, larger cohort studies are warranted to validate the diagnostic value of s-eotaxin-1 level in gastric cancer.

Decreased 5-Hydroxymethylcytosine (5-hmC) is an Independent Poor Prognostic Factor in Gastric Cancer Patients

DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is involved in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Increasing evidence suggests that large-scale loss of 5-hmC is an epigenetic hallmark of several human cancers. However, the value of 5-hmC in diagnosis and prognosis of human cancers, including gastric cancer (GC), remains largely unknown. The aim of this study is to determine 5-hmC levels in GCs and explore its association with clinicopathological characteristics and clinical outcome of GC patients. Using immunohistochemistry (IHC) and dot-blot assays, we demonstrated that 5-hmC was dramatically decreased in GCs compared with matched normal tissues. We also found a strong link between decreased 5-hmC and the reduction of TET1 gene expression, but not TET2 or 3, suggesting that decreased TET1 expression might be one of the mechanisms underlying 5-hmC loss in GCs. Wilcoxon tests showed that 5-hmC content was significantly associated with most of clinicopathological characteristics, such as tumor size (P = 0.016), Bormman type (P < 0.0001), tumor invasion (P = 0.001), TNM stage (P < 0.0001), the number of lymph nodes metastasis (P = 0.002), and survival status (P < 0.0001). It is noteworthy that decreased 5-hmC was significantly associated with poor survival of GC patients. Collectively, our findings indicate that decreased 5-hmC may be crucial to the clinical pathology of GC and is a strong and independent poor prognostic factor in GCs.

Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer

PurposeThe present study is to investigate the clinical utility of tumor marker cutoff ratio (TMR) and develop a TMR combination scoring system based on preoperative tumor marker (TM) levels to prognosis prediction in gastric cancer.MethodsWe include 1,142 patients for whom two or more TMs were measured and who underwent radical gastrectomy between 1990 and 2003.ResultsFive-year risk of recurrence (5 YRR) for carcinoembryonic antigen (CEA) TMRs were 18.3%, 29.8%, 61.4% for TMR < 1.0, 1.0 ≤ TMR < 2.0, TMR ≥ 2.0 respectively. 5 YRR for carbohydrate antigen 19-9 (CA 19-9) TMR were 19.7%, 35.6%, 58.4% for TMR < 1.0, 1.0 ≤ TMR < 3.0, TMR ≥ 3.0, respectively. 5 YRR for carbohydrate antigen 72-4 (CA 72-4) TMR were 15.2% and 33.6% for TMR < 1.0 and TMR ≥ 1.0, respectively. We defined high TMR (TMR ≥ 2.0 for CEA, TMR ≥ 3.0 for CA19-9), low TMR (1.0 ≤ TMR < 2 for CEA, 1.0 ≤ TMR < 3.0 for CA 19-9 and 1.0 ≤ TMR for CA72-4) and negative TMR (TMR < 1.0 for all TMs). A TMR combination scoring system was devised with negative scored as zero points, low as 1 and high as 2 for each TMR. TMR scores were divided into four categories (score 0, 1, 2, 3 and above) based on the calculated TMR score and 5 YRR were found to be 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05). Multivariate analysis showed that our scoring system was a significant independent prognostic factor.ConclusionPreoperative TMRs such as CEA, CA 19-9, and CA 72-4 show a correlation with prognosis and the TMR combination scoring system could be a useful tool for the prediction of prognosis in gastric cancer.

The detection and analysis of serum homocysteine and cystatin C level in patients with malignancy

Objective To investigate the expression of homocysteine and cystatin C in the serum of patients with different types of malignant tumors.Methods 120 patients with malignant tumors were divided into group A (gastric cancer),group B (esophageal canler),group C (liver cancer) and group D (nasopharyngeal carcinoma) according to the type of disease,25 healthy volunteers were selected as control group.Enzyme-linked immunosorbent (ELISA) was used to measure serum homocysteine and cystatin C levels in four groups of patients.Results Homocysteine level of group A,group B,group C and group D were (19.71 ± 3.40)μmol/L,(23.27 ± 9.57)μ mol/L,(21.37 ±0.38) μmol/L and (16.27 ± 1.24) μmol/L,which were significantly higher than those of the control group (all P ＜ 0.05).Cystatin C levels of group A,group B,group C and group D were (19.71 ± 3.40) mg/L,(19.71 ±3.40) mg/L.(19.71 ± 3.40) mg/L and (19.71 ± 3.40) mg/L,which were significantly higher than those of the control group (all P ＜ 0.05).Serum homocysteine and cystatin C levels of gastric cancer positively correlated with carcinoembryonic antigen (CEA) level(r =0.9643,0.9842).However,serum homocysteine and cystatin C levels of esophageal cancer,liver cancer and nasopharyngeal carcinoma had no correlation with serumCEA level.Conclusion Cystatine C and homoeysteine have potential clinical value on the diagnosis of malignant tumors. Key words: Carcinoma; Cystatine; Chalones; Carcinoembryonic antigen; Enzyme-linked immunosorbent assay

LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma

Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide. We investigated the differential expression and putative tumor biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e., LGR4, LGR6, GPR34, GPR160, and GPR171. Based on our previous microarray analyses, we identified five candidate genes in human GC samples. Real-time RT-PCR was carried out to validate their expression in malignant and non-malignant tissues on an independent collective comprising 32 GC patients with and without lymph node metastases. Selected protein targets LGR4 and LGR6 were further validated on paraffin-embedded sections of ten intestinal and ten poorly cohesive (diffuse)-type GCs and their corresponding non-malignant tissue using immunohistochemistry. Additionally, the putative tumor biological significance of LGR4 and LGR6 was studied using tissue microarrays obtained from a cohort of 481 GC patients. On transcriptional level, GPR34, GPR160, and GPR171 were not differentially expressed in GC compared with non-neoplastic mucosa. LGR4 and LGR6 were up-regulated on transcriptional (real-time RT-PCR) and translational (immunohistochemistry) levels in GC. Furthermore, in tissue microarray analysis, LGR6 expression was significantly associated with local tumor growth (T-category; p = 0.04) and correlated with patient survival. LGR4 expression was significantly correlated with nodal spread (N-category; p = 0.025). Our systematic analysis indicates that LGR4 and LGR6 may play a role in GC biology. Future studies will have to demonstrate whether these are also putative diagnostic, prognostic, and/or therapeutic targets for GC.

MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor

Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortality. MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways. In this study, we found that miR-7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function experiments showed that increased miR-7 expression significantly reduced GC cell migration and invasion, whereas decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also demonstrated that overexpression of miR-7 markedly inhibited GC metastasis. Moreover, the insulin-like growth factor-1 receptor (IGF1R) oncogene, which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. Silencing of IGF1R using small interefering RNA (siRNA) recapitulated the anti-metastatic function of miR-7, whereas restoring the IGF1R expression attenuated the function of miR-7 in GC cells. Furthermore, we found that suppression of Snail by miR-7, through targeting IGF1R, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of miR-7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely correlated with IGF1R expression. The present study provides insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. Targeting this novel miR-7/IGF1R/Snail axis would be helpful as a therapeutic approach to block GC metastasis.

Prognostic effects of 25-hydroxyvitamin d levels in gastric cancer.

e14653 Background: Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods: 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results: The mean vitamin D levels of the 197 gastric patients was 49.85±23.68nmol/L, among whom 114(57.9%) were deficient in Vitamin D(&lt;50nmol/L), 67(34%) were insufficient (50-75nmol/L) and 16(8.1%) were sufficient (&gt;75nmol/L). Clinical stage (p=0.004) and lymph node metastasis classification (p=0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥50nmol/L) had a higher overall survival compared with the low vitamin D levels group (&lt;50nmol/L)(p=0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (p=0.019). Conclusions: Vitamin D deficiency may be associated with poor prognosis in gastric cancer.

Mo1574 Clinical Significance of the Preoperative Serum CA 19-9 Level in Gastric Cancer

Mo1574 Clinical Significance of the Preoperative Serum CA 19-9 Level in Gastric Cancer