Levels In Gastric Cancer Research Articles

Abstract 4101: Prognostic significance of LINE-1 mathylation level in gastric cancer

Abstract Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, the LINE-1 methylation level is attracting interest as a useful marker for predicting cancer prognosis. However, the prognostic significance of LINE-1 hypomethylaiton in gastric cancer remains unclear. Methods: Using 96 resected gastric cancer specimens, we quantified the LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for tumor stage. Results: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p<0.0001; N=50). The distribution of the LINE-1 methylation level in the 96 cancers was as follows: mean, 71.0; median, 72.9; SD, 12.2; range, 28.0-97.5; interquartile range, 66.7-77.7 (all in 0-100 scale). LINE-1 methylation level was not associated with tumor stage, T status, or N status (all P>0.05). In univariate analysis, LINE-1 hypermethylation tumor (more than 77.7) tended to have longer overall survival (log-rank p=0.10; univariate HR=0.50, 95% CI 0.19-1.12, p=0.097), although that was not statistically significant. However, in stage-adjusted analysis, LINE-1 hypermethylation was significantly associated with overall survival (HR=0.38, 95% CI 0.14-0.87, p=0.021). Conclusions: LINE-1 hypermethylation in gastric cancer is associated with longer survival, suggesting that it has potential for use as a prognostic biomarker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4101. doi:1538-7445.AM2012-4101

Abstract 2304: MicroRNA-7 functions as antimetastic microRNA in gastric cancer by targeting insulin-like growth factor 1 receptor

Abstract Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and accounts for the majority of cancer-related mortality. MicroRNAs (miRNAs) have been recently emerged as regulators of metastasis through acting on multiple signaling pathways. In this study, we found that miR-7 is significantly down-regulated in high-metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function studies showed that increased miR-7 expression significantly reduced migration and invasion of GC cells, while decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also shown that overexpression of miR-7 remarkably inhibits GC metastasis. Moreover, the IGF1R oncogene, which is often mutated or amplified in human cancers and has been shown to function as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. RNA interference silencing of IGF1R recapitulated the antimetastic function of miR-7, whereas restoration of 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 partly reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of the miR-7 and IGF1R level in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely related to the increase of IGF1R expression. The present study provides an insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. This novel miR-7/IGF1R/Snail axis would be helpful in the therapeutic application to block GC metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2304. doi:1538-7445.AM2012-2304

Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages.

High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

BackgroundResults 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.Methods197 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.ResultsThe mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/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 (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019).ConclusionsVitamin D deficiency may be associated with poor prognosis in gastric cancer.

Serum fatty acid synthase as a marker of gastric neoplasia.

e14543 Background: It is a well-known fact that anaerobiotic metabolism is accelerating in many cancer cells. Lipids seem to be undertaking the important roles of ontogeny and progression. Lipid is made from triglyceride and fatty acid by fatty acid synthase. Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. We have reported that enzyme is overexpressed not only in tissue, but also in serum levels in many cancers. This time, we investigated: (1) the expression of this candidate target in gstric cancer, and (2) the serum level of this enzyme, and considered the possibility of this enzyme for a tumor marker. Methods: (1) Using immunohistochemistry, we evaluated the expression of FAS protein in32 gastric cancers. (2) By using the ElISA kit, we measured the serum level of FAS in 32 patients, who underwent surgical resection ofgastric cancer in Juntendo shizuoka hospital, and 153 normal patients whose samples were provided by cardiologist, Dr. Shimada’s research group. And we considered the relationship with pathological stage and clinical data. Results: (1) We discovered significantly higher levels of FAS expression in 77% of gastric cancers. (2) The serum FAS levels were also significantly higher control (patient’s average is 23.0 ug/mL, and control is 2.3ul/mL). There is no significant correlation with clinicopathological data. Conclusions: Similar to several other common types of human cancer, FAS is expressed at very high levels in gastric cancer. The serum FAS level is also expressed at significantly high levels in human gastric carcinomas. It appears that the FAS serum level will be a tumor marker candidate.

Stem Cell Associated Genes Working with One MiRNA Cluster Have Different Clinic Pathologic Values in Gastric Cancer

Cancer stem cells are nowadays considered to be the origin of cancer. Also, stem cell associated genes are emerging as predictors of cancer malignancy. We investigated the association of several stemness genes (c-Myc, PTEN, p57 and p21) with clinic pathological parameters and survival in stomach cancer by performing immunohistochemistry on paraffin sections of gastric cancer patients who underwent surgical staging with following-up statistics. We discovered that expression of c-Myc was significantly related to distant metastasis, the combined expression of PTEN and p21 correlated positively to overall survival, while p57 was less useful in overall survival prediction in gastric cancer. Additionally, there is a positive correlation between expressions of p57 and p21. In conclusion, our present study indicated that expression of stemness genes (c-Myc, PTEN, p57 and p21) performed different predictive potential in the evaluation of clinical malignancy levels in gastric cancer.

MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2

Emerging evidence has shown the association of aberrantly expressed microRNAs (miRNAs) with tumor development and progression. However, little is known about the potential role of miRNAs in gastric carcinogenesis. Here, we performed miRNA microarray to screen miRNAs differentially expressed in the paired gastric cancer and their adjacent nontumor tissues and found that miR-375 was greatly downregulated in gastric cancer tissues. Quantitative real-time PCR analysis verified that miR-375 expression was significantly decreased in more than 90% of primary gastric cancers compared with their nontumor counterparts from patients undergoing gastric resection. Overexpression of miR-375 significantly inhibited gastric cancer cell proliferation in vitro and in vivo. Forced expression of miR-375 in gastric cancer cells significantly reduced the protein level of Janus kinase 2 (JAK2) and repressed the activity of a luciferase reporter carrying the 3'-untranslated region of JAK2, which was abolished by mutation of the predicted miR-375-binding site, indicating that JAK2 may be a miR-375 target gene. Either inhibition of JAK2 activity by AG490 or silencing of JAK2 by RNAi suppressed gastric cancer cell proliferation resembling that of miR-375 overexpression. Moreover, ectopic expression of JAK2 can partially reverse the inhibition of cell proliferation caused by miR-375. Finally, we found a significant inverse correlation between miR-375 expression and JAK2 protein level in gastric cancer. Thus, these data suggest that miR-375 may function as a tumor suppressor to regulate gastric cancer cell proliferation potentially by targeting the JAK2 oncogene, implicating a role of miR-375 in the pathogenesis of gastric cancer.

The Potential for Serum p53 to Predict the Response to Chemotherapy of Patients with Gastric Cancer

This study was designed to investigate the relationship between serum p53, tissue p53 and tissue permeability glycoprotein (P-gp) levels in gastric cancer. Serum levels of p53 were detected by enzyme-linked immunosorbent assay, and tissue p53 and P-gp levels were analysed by immunohistochemistry. In total, 63.0% of gastric cancer tissue samples tested positive for P-gp and 58.7% of samples tested positive for p53. Tissue P-gp immunoreactivity was significantly correlated with tissue p53 immunoreactivity, and both tissue p53 and P-gp immunoreactivity were significantly correlated to the degree of cancer cell differentiation. The percentage of gastric cancer patients with serum positive for p53 was 36.2%, which was significantly higher than the rate in non-cancerous gastric disease patients. Serum p53 was significantly correlated to tissue p53 and tissue P-gp, inferring that the presence of p53 in the serum could indicate the status of tissue p53 and P-gp. This could, therefore, be useful for screening for the most appropriate (lowest toxicity and highest effectiveness) drugs to use ahead of (neo)-adjuvant chemotherapy.

Prognostic Role of Estrogen Receptor α and Estrogen Receptor β in Gastric Cancer

The presence of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) have been reported in cell and tissue level in gastric cancer, but its impact on patients' survival remains unclear. This study was designed to investigate the expression level of ERalpha and ERbeta and to assess clinical significance of ERalpha and ERbeta expression in gastric cancer. The expression level of ERalpha and ERbeta were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) in 35 surgically resected gastric cancer and corresponding normal tissues and by immunohistochemical staining in 211 surgically resected gastric cancer and match normal tissues. The expression level between ERalpha mRNA expression in gastric cancer tissues and match normal tissues had no statistically significant difference. The ERbeta mRNA level in normal tissues was significantly higher than that observed in gastric cancer tissues (P = 0.001). Neither ERalpha nor ERbeta mRNA expression levels had significant correlation with clinicopathologic parameters. Forty-eight of 211 (22.7%) gastric cancer tissues showed positive expression of ERalpha and ERbeta detected in gastric cancer. ERalpha-positive expression correlated with poorer overall survival (P = 0.014), as did the absence of ERbeta expression in patients with gastric cancer (P = 0.001). In multivariate analysis, the positive expression of ERalpha and the absence of ERbeta were significant independent prognostic factors for overall survival (hazard ratio 2.159, P = 0.013, and hazard ratio 2.016, P = 0.025 respectively). Our results indicated that ERalpha and ERbeta were expressed in both gastric cancer and corresponding normal tissues. ERalpha expression and the absence of ERbeta expression are associated with poor survival.

FAT10 level in human gastric cancer and its relation with mutant p53 level, lymph node metastasis and TNM staging

To investigate the role of FAT10 and mutant p53 in the pathogenesis, severity and prognosis of gastric cancer. FAT10, mutant p53 mRNA and protein levels were measured by reverse transcription (RT)-PCR and immunohistochemistry in gastric cancer tissue (n = 62), tumor-adjacent tissue (n = 62) and normal gastric tissue (n = 62). Relation of FAT10 and mutant p53 expression with clinicopathological features and clinical outcomes of gastric cancer patients were analyzed. The FAT10, mutant p53 mRNA and protein levels were significantly higher in gastric cancer than in its adjacent and normal tissue. The FAT10 and mutant p53 levels in gastric cancer tissue were significantly correlated with lymph node metastasis and tumor, nodes, metastasis (TNM) staging. Moreover, the high FAT10 level was associated with the overall survival rate of patients. Multivariate Cox-proportional hazards model analysis showed that mRNA and protein levels of FAT10 and mutant p53, lymph node metastasis, distant metastasis and TNM stage were the independent prognostic factors for gastric cancer. FAT10 may be involved in gastric carcinogenesis, and is a potential marker for the prognosis of gastric cancer patients. FAT10 and mutant p53 may play a common role in the carcinogenesis of gastric cancer.

Detection of Serum Gastric Cancer-Associated MG7-Ag from Gastric Cancer Patients Using a Sensitive and Convenient ELISA Method

Purpose: To seek a high sensitive and convenient method for early diagnosis of gastric cancer by testing MG7-Ag in serum of gastric cancer patients and some other control groups using a convenient ELISA method. Experiment Design: The expression of serum MG7-Ag was detected in 116 preoperative gastric cancer patients, 63 postoperative gastric cancer patients, 78 precancerous lesion patients, 50 healthy blood donors and patients of other cancers by a convenient ELISA method. For comparison, serum CEA, CA 50, CA 19-9 and TAG-72 were also detected in preoperative gastric cancer patients. Meanwhile, the expression of MG7-Ag was detected by immunohistochemical analysis in the groups of patients with gastric cancer or precancerous lesion mentioned above. Results: The positive rate of Mg7-Ag determined by ELISA was 83. 6% of preoperative gastric cancer patients, 54.8% of lung cancer patients, 45.5% of rectal cancer patients, 17.6% of colonic cancer patients, 14.2% of breast cancer patients, 47.6% of postoperative gastric cancer patients, 12.8% of precancerous lesions patients and 0% of healthy blood donors, respectively. The sensitivity of ELISA (83.6%) was found to be similar with that of immunohistochemistry (94%, p > 0. 01), while the false positive rate was lower (12.8% vs. 51.3%). MG7-Ag expression level in gastric cancer was correlated with tumor differentiation (p < 0. 01) and pathological stage (p < 0. 01). Conclusion: This ELISA method may be a non-invasive candidate method for screening of large population with high risk of gastric cancer.

Prognostic value of preoperative CEA, CA 19-9, CA 72-4, and AFP levels in gastric cancer

Recent research has suggested that serum tumor markers can give valuable prognostic information in gastric cancer. In this study, we examined the relationship between preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 72-4, and alfa fetoprotein (AFP) levels on clinicopathologic significance in gastric cancer patients. Preoperative plasma levels of CEA, CA 19-9, CA 72-4, and AFP were retrospectively examined in 95 patients who underwent surgical resection for gastric cancer, and the prognostic value of the tumour markers were estimated. The percentage of CA 19-9, CA 72-4, CEA, and AFP-positive cases were 41%, 32.6%, 24.2%, and 8.4%, respectively. CEA was more frequently positive in the patients with liver metastases (P=0.02). CA 19-9 was more frequently positive in patients with lymph node (P=0.005), peritoneal (P=0.01), and serosal (P=0.03) involvement. CA 72-4 was more frequently positive in patients with lymph node (P=0.01), peritoneal (P=0.03), and liver (P=0.01) involvement. Low 3-year cumulative survival was associated significantly with elevated serum levels of CEA (P=0.001), CA 19-9 (P=0.001), CA 72-4 (P=0.001), and AFP (P=0.01). In multivariate analysis, age, tumor stage, and CA 72-4 were the only independent prognostic factors. Being positive for CA 72-4 was associated with a 3.8-fold higher risk of death (95% confidence intervals: 1.3, 10.9). Our results suggest that high preoperative serum levels of CA 72-4 in gastric cancer patients are associated with a higher risk of death due to gastric cancer.

Clinicopathologic significance of hypoxia-inducible factor 1α, p53, and vascular endothelial growth factor expression and preoperative serum vascular endothelial growth factor level in gastric cancer

4576 Backgrounds: Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer. Methods: We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF). Results: The positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (p=0.015, p=0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (p=0.005, p=0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (p=0.013, p=0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF, VEGF, and p53 were not observed. The median follow- up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (p=0.002). Conclusion: p53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease progression in patients with gastric cancers. No significant financial relationships to disclose.

Clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer

BackgroundHypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).ResultsThe positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (P = 0.015, P = 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P = 0.010, P = 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1α, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).Conclusionp53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.

Elevated serum level and gene polymorphisms of TGF‐β1 in gastric cancer

Transforming growth factor (TGF)-beta1, as a candidate tumor marker, is currently of interest. In this study, serum TGF-beta1 levels in gastric cancer (GC) patients and healthy volunteers were measured using enzyme-linked immunosorbent assay (ELISA). In addition, single nucleotide polymorphisms (SNPs) of the TGF-beta1 gene at codon 10 and codon 25 were identified by means of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and sequence analysis. Our results indicated that serum concentrations of TGF-beta1 in GC patients were significantly higher than those in the control, and positively correlated with tumor mass, invasion, metastasis, and clinical stage. The serum TGF-beta1 levels of patients recovering from radical resection were markedly lower than those before surgery. Meanwhile, no deoxyribonucleic acid (DNA) sequence variation at codon 25 of the TGF-beta1 gene was found and a TGF-beta1 gene polymorphism at codon 10 did not show obvious correlations with either TGF-beta1 expression or clinicopathological parameters of GC. Our evidence suggested that serum concentration of TGF-beta1 might be a novel tumor marker for GC and the polymorphisms of TGF-beta1 gene did not play a role as a determinant of serum TGF-beta1 concentration or as a genetic risk factor in the gastric carcinogenesis and progression.

Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

Transforming growth factor-β1 (TGF-β1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-β1 activation and localisation of TGF-β1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-β1 staining by immunohistochemistry. Active TGF-β1 was present in malignant epithelial cells, but most strongly in smooth muscle actin expressing fibroblasts. Normal gastric mucosa from the same patient showed some staining for total, and little for active TGF-β1. Active TGF-β1 levels were determined by ELISA on tissue homogenates, confirming a strong increase in active TGF-β1 in tumours compared to corresponding normal mucosa. Moreover, high tumour TGF-β1 activity levels were significantly associated with clinical parameters, including worse survival of the patients. Total and active TGF-β1 levels were not correlated, suggesting a specific activation process. Of the different proteases tested, active TGF-β1 levels were only correlated with urokinase activity levels. The correlation with urokinase activity suggests a role for plasmin in TGF-β1 activation in the tumour microenvironment, resulting in transformation of resident fibroblasts to tumour promoting myofibroblasts. In conclusion we have shown localisation and clinical relevance of TGF-β1 activity levels in gastric cancer.

Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein

The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein.

Identification of genes with correlated patterns of variations in DNA copy number and gene expression level in gastric cancer

To identify DNA copy number changes that had a direct influence on mRNA expression in gastric cancer, cDNA microarray-based comparative genomic hybridization (aCGH) and gene expression profiling were performed using 17 K cDNA microarrays. A set of 158 genes showing Pearson correlation coefficients over 0.6 between DNA copy number changes and mRNA expression level variations was selected. In an independent gene expression profiling of 60 tissue samples, the 158 genes were able to distinguish most of the normal and tumor tissues in an unsupervised hierarchical clustering, suggesting that the differential expression patterns displayed by this specific group of genes are most likely based on the gene copy number changes. Furthermore, 43 statistically significant ( P < 0.01) genes were selected that correctly distinguished all of the tissue samples. The copy number changes detected by aCGH can be verified by fluorescence in situ hybridization and real-time polymerase chain reaction. The selected genes include those that were previously identified as being tumor suppressors or deleted in various tumors, including GATA binding protein 4 (GATA4), monoamine oxidase A (MAOA), cyclin C (CCNC), and oncogenes including malignant fibrous histiocytoma amplified sequence 1 (MFHAS1/MASL1), high mobility group AT-hook 2 (HMGA2), PPAR binding protein (PPARBP), growth factor receptor-bound protein 7 (GRB7), and TBC1 (tre-2, BUB2, cdc16) domain family, member 1 (TBC1D1).

Relationship between preoperative staging by endoscopic ultrasonography and MMP-9 expression in gastric carcinoma

To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma. Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA), while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues. The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%. Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer (P<0.05). The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9. The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high, physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.