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Expression of tumor related genes NGX6, NAG-7, BRD7 in gastric and colorectal cancer.

ABSTRACT: AIM:NGX6, NAG-7 and BRD7 genes are tumor related genes, which have been newly cloned by positional candidate cloning strategy. This study was designed to investigate the expression levels of NGX6, NAG-7 and BRD7 genes in human gastric and colorectal cancer tissues, and their corresponding normal tissues, and to investigate whether these genes play a role in the pathogenesis of gastric and colorectal cancers. METHODS:Reverse transcription-polymerase chain reaction (RT-PCR), dot hybridization and Northern blot analysis were used to compare the expression levels of NGX6, NAG-7 and BRD7 genes in 34 gastric cancer tissues and 34 colorectal cancer tissues with their corresponding normal tissues of the same patients, respectively. RESULTS:Among the 34 colorectal cancer specimens and the 34 gastric cancer specimens, the expression of NGX6 in 25 colorectal cancer tissues was absent or very weak (73.5 %) by RT-PCR analysis. The down-regulation rate of NGX6 in colorectal cancer tissues was significantly higher than that in corresponding normal tissues (26.5 %,9/34) (P<0.005). Moreover, the down-regulation of NGX6 was significantly correlated with lymph node and/or distance metastases. Patients with lymph node and/or distance metastasis had much higher down-regulation rate of NGX6 than patients without metastases (93.8 % vs 55.6 %, P<0.05). However no correlation was found between the expression of NGX6 and pathologic type of colorectal cancer in this study, and also the expression of NGX6 did not display any difference between gastric cancer and corresponding normal tissues (58.8 % vs 70.6 %, P>0.25). Dot hybridization and Northern blot analysis confirmed the results of RT-PCR. Furthermore, NAG-7 and BRD7 mRNA was not up- or down-regulated in gastric and colorectal cancers compared with their corresponding normal tissues in our study. CONCLUSION:The down-regulation of NGX6 may be closely associated with tumorigenesis and metastasis of colorectal carcinoma. However, it may not contribute to the development and progression of gastric carcinoma. In addition, the expression levels of NAG-7, and BRD7 did not alter in gastric and colorectal cancers. This seems to suggest that NAG-7 and BRD7 genes may not play a role in gastric and colorectal carcinogenesis.

SUBMITTER: Zhang XM

PROVIDER: S-EPMC4611532 | biostudies-literature | 2003 Aug

REPOSITORIES: biostudies-literature

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Expression of tumor related genes NGX6, NAG-7, BRD7 in gastric and colorectal cancer.

Zhang Xiao-Mei XM Wang Xiao-Yan XY Sheng Shou-Rong SR Wang Jie-Ru JR Li Jiang J

World journal of gastroenterology 20030801 8

<h4>Aim</h4>NGX6, NAG-7 and BRD7 genes are tumor related genes, which have been newly cloned by positional candidate cloning strategy. This study was designed to investigate the expression levels of NGX6, NAG-7 and BRD7 genes in human gastric and colorectal cancer tissues, and their corresponding normal tissues, and to investigate whether these genes play a role in the pathogenesis of gastric and colorectal cancers.<h4>Methods</h4>Reverse transcription-polymerase chain reaction (RT-PCR), dot hyb ...[more]

PMID: 12918109

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Project description:Background: Ferroptosis is a form of regulated cell death that occurs as a consequence of lethal lipid peroxidation. A wealth of studies has demonstrated that ferroptosis profoundly modulated numerous biological behaviors of tumor. However, its natural functions in gastric cancer (GC) remain to be explored. Methods: Firstly, a total of over 1,000 GC patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database were included in our study. Secondly, 32 ferroptosis-related genes were extracted from the ferrDb website. Then, unsupervised clustering was performed to classify patients into three distinct ferroptosis-related clusters. Subsequently, we systematically and comprehensively explored the biological characteristics of each cluster. Finally, we constructed a scoring system, named ferroptosis score, to quantify each cluster and also investigated the predictive therapeutic value of the ferroptosis score for chemotherapy and immunotherapy. Results: Based on the expressions of 32 ferroptosis-related genes, three distinct ferroptosis-related subtypes with various biological characteristics were determined. Integrated analysis showed that cluster 1 is a microsatellite instability (MSI)-like subtype, cluster 2 is an epithelial-mesenchymal transition (EMT)-like subtype, while cluster 3 tends to be a metabolic-like subtype. Prognostic analysis revealed that patients in cluster 2 had a worse overall survival and relapse-free survival. The distribution of the ferroptosis score was significantly different in clusters and gene clusters. The ferroptosis score could predict the biological characteristics of each cluster, the stromal activity, and progression of tumor. The low ferroptosis score group was characterized by the activation of antigen processing and presentation, DNA damage repair pathways, and metabolic pathways, while the high ferroptosis score group was characterized by stromal activation. In response to anticancer drugs, the ferroptosis score was highly negatively associated with drugs targeting MAPK signaling and PI3K/mTOR signaling, while it was positively correlated with drugs targeting the cell cycle, mitosis, and metabolism. Finally, we also proved that the ferroptosis score could serve as a reliable biomarker to predict response to immunotherapy. Conclusion: This work revealed that tumor cells and their surrounding microenvironment could be shaped by varying the activation degrees of ferroptosis. Establishing ferroptosis-related subtypes would guide in predicting the biological features of individual tumors and selecting appropriate treatment protocols for patients.

Project description:BackgroundNasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). In this study, we explored the role of DNA methylation in regulation of NGX6 transcription.MethodsIn the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation.ResultsThe sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P < 0.05). An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the NGX6 promoter was associated with colorectal cancer patients age (P < 0.05). Moreover, a trend was shown toward metastasis status and primary site in colorectal carcinomas with NGX6 promoter methylation (p = 0.056 and P = 0.067, respectively). In addition, 5-Aza-dC could induce NGX6 mRNA expression and NGX6 promoter demethylation in HT-29 cells.ConclusionsDown-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.

Dataset Information

Expression of tumor related genes NGX6, NAG-7, BRD7 in gastric and colorectal cancer.

Publications

Expression of tumor related genes NGX6, NAG-7, BRD7 in gastric and colorectal cancer.

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