Expression and Clinical Significance of ILF2 in Gastric Cancer.
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ABSTRACT:
SUBMITTER: Yin ZH
PROVIDER: S-EPMC5555027 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:AIM:To determine the correlation between methylation status of 5' CpG island of cyclooxygenase-2 (COX-2) gene and protein expression in gastric cancer tissues for distinguishing the molecular characters of gastric cancers. METHODS:Methylation status of 5' CpG island of COX-2 gene was studied by PCR amplification after HpaII and Hha I restrictive enzyme digestion; COX-2 expression was evaluated by immunohistochemical method. RESULTS:Hpa II and HhaI site were all methylated in 12 normal gastric mucosa tissues, whereas they were demethylated in 77.27% (34/44) and 84.09% (37/44) gastric cancer tissues, respectively. Expression of COX-2 was detected in 68.18% (30/44) gastric cancer tissues, but no expression was found in normal gastric mucosa tissues. In gastric cancer tissues, COX-2 expression was correlated significantly with HpaII site demethylation (29/30 vs 5/14, P<0.001 and HhaI site demethylation (28/30 vs 9/14, P<0.05). CONCLUSION:The demethylation of 5' CpG island of gene is necessary for COX-2 expression in human gastric cancer. The expression status of COX-2 may provide theoretical basis for COX-2 targeting gastric cancer treatments.
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Project description:BackgroundGastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC.Materials and methodsThe expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored.Resultshsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n = 100, p < 0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p = 0.001), TNM stage (p = 0.013), and lymphatic metastasis (p = 0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p = 0.047).Conclusionhsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).
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Project description:PurposeIsoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC).Materials and methodsWe evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017.ResultsCLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival.ConclusionsCLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.
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Project description:Chromodomain helicase DNA-binding 5 (CHD5), which is a member of the CHD family, has been identified as a tumor suppressor gene in a variety of malignancies. The aim of the current study was to clarify the clinical significance of CHD5 expression in gastric cancer. CHD5 expression was evaluated using immunohistochemistry (IHC) in 154 specimens resected from patients with gastric cancer from January 2011 to December 2013, and assessed its relationships with clinicopathological characteristics and survival. In vitro cell proliferation, invasion, and migration assays and western blotting analysis were performed to clarify the role of CHD5 in human gastric cancer cell lines. Of a total of 154 patients, 57 (37.0%) exhibited low CHD5 expression, which was significantly associated with positive lymphatic invasion (P=0.032), advanced pT status (P=0.011), and advanced pStage (P=0.014). Overall survival (OS) in patients with low CHD5 expression was significantly worse compared with patients with high CHD5 expression (hazard ratio, 1.96; 95% confidence interval, 1.09-3.45; log-rank P=0.023). Cox multivariate analysis for OS revealed that CHD5 expression was an independent prognostic factor with age and pN status. In vitro, the upregulation of CHD5 in gastric cancer cells with low CHD5 expression significantly decreased cell proliferation, migration and invasion. CHD5 was associated with the regulation of multiple cancer-related targets, including p53 and enhancer of zeste homolog 2 (EZH2) in western blotting analysis. In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer.
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Project description:BACKGROUND:Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. METHODS:The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. RESULTS:Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. CONCLUSIONS:All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer.
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Project description:Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.
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Project description:BACKGROUND: We aimed to detect CD40 mutant expression and evaluate its clinical significance in gastric cancer. METHODS: CD40 mutant expression in 78 cases of gastric cancer tissues, 10 cases of normal gastric tissues, and 10 cases of gastric adenoma tissues by immunohistochemical test. Survival analyses were also performed. RESULTS: The positive CD40 mutant rate in gastric cancer was 55.1% (43/78). No positive CD40 mutant staining was observed in the normal gastric tissue or the gastric adenoma. CD40 mutants expression was significantly correlated with invasive depth, lymph metastasis, and TNM stage (P <0.05). Cases with negative CD40 mutant expression had a significantly longer median survival time than those with positive CD40 mutant expression (40 vs. 14 months, P <0.05). A lower death risk in negative CD40 mutant cases was observed comparing with positive CD40 mutant cases. CONCLUSIONS: Positive CD40 mutant expression suggests a poorer prognosis of gastric cancer cases.
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Project description:The aim of the present study was to investigate the expression and clinicopathological features of matrix metalloproteinase 17 (MMP17; also known as MT4-MMP) and MMP25 (also known as MT6-MMP) in gastric cancer. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression of MMP17 and MMP25 in 42 cases of gastric carcinoma and normal tissues, and 40 cases of atrophic gastritis. The expression of MMP17 in the normal gastric and atrophic gastritis tissues was significantly lower than that in the gastric cancer tissues (P<0.05). The expression of MMP25 in the gastric cancer and atrophic gastritis tissues was markedly higher compared with the normal gastric tissues (P<0.05). The expression of MMP17 and MMP25 was significantly associated with the depth of tumor invasion, lymph node metastasis and serous membrane involvement (P<0.05), but not with patient age and gender, or lesion length, site and histological grade (P>0.05). Therefore, this indicates that the expression of MMP17 and MMP25 is increased with the degree of progress of gastric carcinoma. The detection of MMP17 and MMP25 expression may have clinical value in predicting the prognosis of patients with gastric cancer.
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Project description:Circular RNAs (circRNAs) are a new class of noncoding RNAs. However, the expression profile and clinical significance of circRNAs in human gastric cancer is unclear. The global circRNA expression profile in human gastric cancer was measured by circRNA microarray. Hsa_circ_0014717, one of the most downregulated circRNAs in microarray, was selected as a targeted circRNA to explore its levels in gastric tissues and gastric juice. Freeze-thaw experiment and incubation experiment confirmed the stability of gastric juice circRNAs. A total of 308 circRNAs, including 107 (34.74%) upregulated and 201 (65.26%) downregulated circRNAs, were found significantly aberrantly expressed in gastric cancer tissues. The top ten upregulated in gastric cancer tissues were hsa_circ_0035445, hsa_circ_0003789, hsa_circ_0063809, hsa_circ_0074362, hsa_circ_0006282, hsa_circ_0011107, hsa_circ_0084606, hsa_circ_0005556, hsa_circ_0050547, and hsa_circ_0006470, while the top ten downregulated ones were hsa_circ_0007099, hsa_circ_0001897, hsa_circ_0007707, hsa_circ_0008832, hsa_circ_0001546, hsa_circ_0002089, hsa_circ_0004680, hsa_circ_0000154, hsa_circ_0004458, and hsa_circ_0008394. The hot-point chromosomes were chr1, chr2, chr3, chr9, and chr17. Hsa_circ_0014717 was significantly downregulated in 77.2% (74/96) gastric cancer tissues. Its levels in gastric cancer tissues were related to tumor stage (P = 0.037), distal metastasis (P = 0.048), tissue carcinoembryonic antigen (P = 0.001), and carbohydrate antigen 19-9 expression (P = 0.021). More importantly, hsa_circ_0014717 can stably exist in human gastric juice; and its nature meets the requirements of clinical detection. Our study uncovered the circRNA expression profile in human gastric cancer. Moreover, some circRNAs can stably exist in human body fluid, and has the potential to be used as novel biomarkers for the screening of high-risk gastric cancer patients.
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Project description:BackgroundGastric cancer (GC) is one of the common gastrointestinal malignancy worldwide and exhibits a poor prognosis. Increasing studies have indicated that microRNAs play critical roles in the cancer progression and have shown great potential as useful biomarkers. The search for potential diagnostic and prognostic biomarkers of gastric cancer (GC) with integrated bioinformatics analyses has been undertaken in previous studies.MethodsIn this study, the robust rank aggregation (RRA) method was used to perform an integrated analysis of differentially expressed miRNAs (DEMs) from five microarray datasets in the Gene Expression Omnibus (GEO) database to find robust biomarkers for GC. Ultimately, seven miRNAs were filtered from fourteen primary miRNAs using the validation set of The Cancer Genome Atlas (TCGA) database. Based on these results, diagnostic and survival analyses were performed, and logistic regression and Cox regression were used to determine the clinicopathological characteristics of the DEM expression and overall survival.ResultsNine eligible miRNA datasets related to GC were selected from the GEO database for integrated analysis in this study. Diagnostic analysis implied that these miRNAs could be regarded as promising candidate diagnostic biomarkers in GC tissues, but whether the results of the tissue analysis are consistent with those of peripheral blood analysis requires further validation. The logistic regression indicated that the ectopic expression of these DEMs was relevant to the histological type, anatomical region, and pathological grade of GC. However, the survival and Cox regression analyses suggested that the poor prognosis of GC patients was not strongly dependent on the ectopic expression of the seven miRNAs, but rather, a poor prognosis was associated with age, metastasis, and histological grade.ConclusionsBased on the results presented in this study it can be concluded that these miRNAs (miR-455-3p, miR-135b-5p, let-7a-3p, miR-195-5p, miR-204-5p, miR-149-5p, and miR-143-3p) might be potential biomarkers for the early diagnosis of GC patients, but this finding should be regarded with caution. A large-scale, prospective, and multicenter cohort study should be performed.
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