scholarly journals Combined bioinformatics technology to explore pivot genes and related clinical prognosis in the development of gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiasheng Xu ◽  
Xinlu Wang ◽  
Qiwen Ke ◽  
Kaili Liao ◽  
Yanhua Wan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Stage ◽  
Ppi Network ◽  
Clinical Prognosis ◽  
Normal Tissues ◽  
Cancer Related Gene ◽  
Key Genes ◽  
Cancer Tissues ◽  
Differential Genes ◽  
Development Of Gastric Cancer

AbstractTo screen the key genes in the development of gastric cancer and their influence on prognosis. The GEO database was used to screen gastric cancer-related gene chips as a training set, and the R packages limma tool was used to analyze the differential genes expressed in gastric cancer tissues compared to normal tissues, and then the selected genes were verified in the validation set. The String database was used to calculate their Protein–protein interaction (PPI) network, using Cytoscape software's Centiscape and other plug-ins to analyze key genes in the PPI network. The DAVID database was used to enrich and annotate gene functions of differential genes and PPI key module genes, and further explore correlation between expression level and clinical stage and prognosis. Based on clinical data and patient samples, differential expression of key node genes was verified by immunohistochemistry. The 63 characteristic differential genes screened had good discrimination between gastric cancer and normal tissues, and are mainly involved in regulating extracellular matrix receptor interactions and the PI3k-AKT signaling pathway. Key nodes in the PPI network regulate tumor proliferation and metastasis. Analysis of the expression levels of key node genes found that relative to normal tissues, the expression of ITGB1 and COL1A2 was significantly increased in gastric cancer tissues, and patients with late clinical stages of tumors had higher expression of ITGB1 and COL1A2 in tumor tissues, and their survival time was longer (P < 0.05). This study found that ITGB1 and COL1A2 are key genes in the development of gastric cancer and can be used as prognostic markers and potential new targets for gastric cancer.

scholarly journals SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Gastric Cancer Cells ◽  
Anion Transporter ◽  
Transporter Family ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

scholarly journals The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Western Blot ◽  
Clinical Significance ◽  
Normal Mucosa ◽  
Normal Tissues ◽  
Positive Rate ◽  
Her 2 ◽  
Cancer Tissues ◽  
Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

scholarly journals miR-1915-3p inhibits Bcl-2 expression in the development of gastric cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Hong-wei Cui ◽  
Wen-yan Han ◽  
Li-na Hou ◽  
Ling Yang ◽  
Xian Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Kidney Diseases ◽  
B Cell Lymphoma ◽  
Gene Expressions ◽  
Gastric Cancer Cells ◽  
Apoptotic Protein ◽  
Gastric Cancer Stem Cells ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Abstract Many gene expressions changed during the development of gastric cancer, and non-coding RNAs including microRNAs (miRNAs) have been found to regulate cancer progression by participating in the process of tumor cell growth, migration, invasion and apoptosis. Our previous study has identified 29 miRNAs that are highly expressed in gastric cancer stem cells. One of these miRNAs, miR-1915-3p, has shown great potential as a diagnostic and prognostic biomarker for the cancers in liver, colon and thyroid, as well as in immune and kidney diseases. Herein, we found that miR-1915-3p exhibited low expression level in differentiated gastric cancer cell lines and gastric cancer tissues. It was found that the miR-1915-3p inhibited the growth of gastric cancer cells and thus promoted cell apoptosis. We discovered that the expressions of miR-1915-3p were significantly correlated to the lymph node metastasis and overall survival of patients with gastric cancer. Further study showed that there was a negative correlation between miR-1915-3p and Bcl-2 (B cell lymphoma/leukemia-2) expression, suggesting that Bcl-2 was a target gene of miR-1915-3p. Hence, miR-1915-3p possibly contributes to the development and progression of gastric cancer by inhibiting the anti-apoptotic protein Bcl-2. The finding provides a potential therapeutic strategy for gastric cancer.

scholarly journals CLIC4 abrogation promotes epithelial–mesenchymal transition in gastric cancer

2019 ◽  
Vol 41 (6) ◽  
pp. 841-849 ◽  
Author(s):  
Baolong Wang ◽  
Jiqing Zheng ◽  
Qiongyuan Chen ◽  
Chaofan Wu ◽  
Yangxin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Stage ◽  
Stem Cell Markers ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers ◽  
Normal Tissues ◽  
Gastric Adenocarcinomas ◽  
Etoposide Treatment

Abstract Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial–mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

scholarly journals Bioinformatics analysis for the identification of differentially expressed genes and related signaling pathways in H. pylori-CagA transfected gastric cancer cells

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11203
Author(s):  
Dingyu Chen ◽  
Chao Li ◽  
Yan Zhao ◽  
Jianjiang Zhou ◽  
Qinrong Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Differentially Expressed Genes ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Ags Cells ◽  
Kegg Pathway Analysis ◽  
Key Genes

Aim Helicobacter pylori cytotoxin-associated protein A (CagA) is an important virulence factor known to induce gastric cancer development. However, the cause and the underlying molecular events of CagA induction remain unclear. Here, we applied integrated bioinformatics to identify the key genes involved in the process of CagA-induced gastric epithelial cell inflammation and can ceration to comprehend the potential molecular mechanisms involved. Materials and Methods AGS cells were transected with pcDNA3.1 and pcDNA3.1::CagA for 24 h. The transfected cells were subjected to transcriptome sequencing to obtain the expressed genes. Differentially expressed genes (DEG) with adjusted P value < 0.05, — logFC —> 2 were screened, and the R package was applied for gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The differential gene protein–protein interaction (PPI) network was constructed using the STRING Cytoscape application, which conducted visual analysis to create the key function networks and identify the key genes. Next, the Kaplan–Meier plotter survival analysis tool was employed to analyze the survival of the key genes derived from the PPI network. Further analysis of the key gene expressions in gastric cancer and normal tissues were performed based on The Cancer Genome Atlas (TCGA) database and RT-qPCR verification. Results After transfection of AGS cells, the cell morphology changes in a hummingbird shape and causes the level of CagA phosphorylation to increase. Transcriptomics identified 6882 DEG, of which 4052 were upregulated and 2830 were downregulated, among which q-value < 0.05, FC > 2, and FC under the condition of ≤2. Accordingly, 1062 DEG were screened, of which 594 were upregulated and 468 were downregulated. The DEG participated in a total of 151 biological processes, 56 cell components, and 40 molecular functions. The KEGG pathway analysis revealed that the DEG were involved in 21 pathways. The PPI network analysis revealed three highly interconnected clusters. In addition, 30 DEG with the highest degree were analyzed in the TCGA database. As a result, 12 DEG were found to be highly expressed in gastric cancer, while seven DEG were related to the poor prognosis of gastric cancer. RT-qPCR verification results showed that Helicobacter pylori CagA caused up-regulation of BPTF, caspase3, CDH1, CTNNB1, and POLR2A expression. Conclusion The current comprehensive analysis provides new insights for exploring the effect of CagA in human gastric cancer, which could help us understand the molecular mechanism underlying the occurrence and development of gastric cancer caused by Helicobacter pylori.

scholarly journals High Expression of Nucleobindin-2 Is Associated With Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1021-A1021
Author(s):  
Junichi Okada ◽  
Eijiro Yamada ◽  
Tsugumichi Saito ◽  
Yasuyo Nakajima ◽  
Atsushi Ozawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Leucine Zipper ◽  
Independent Predictor ◽  
Clinical Stage ◽  
High Expression ◽  
Peripheral Tissues ◽  
Tumor Tissues ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163 and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. NUCB2 was also identified as a potential tumor antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. However, theclinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

scholarly journals miR-301-3p directly regulates Cx43 to mediate the development of gastric cancer

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110331
Author(s):  
Shasha Liu ◽  
Yang Zhao ◽  
Huan Liu ◽  
Xing Zhao ◽  
Xingbin Shen
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Clinical Prognosis ◽  
Expression Levels ◽  
Reporter Assays ◽  
Cx43 Mrna ◽  
Development Of Gastric Cancer

Objective Identifying novel biomarkers involved in the development of gastric cancer (GC) can provide potential therapeutic strategies and improve clinical prognosis. miR-301-3p and Cx43 are reportedly dysregulated in GC. miR-301-3p and Cx43 interaction, and their functions in GC progression, are still poorly understood. Methods The expression levels of miR-301-3p and Cx43 in GC tissues and cell lines with various differentiation degrees were evaluated by RT-qPCR. The interaction between miR-301-3p and Cx43 was assessed by dual-luciferase reporter assays. CCK8 and Transwell assays were employed to assess the effects of the miR-301-3p- Cx43 axis on GC cell proliferation, migration, and invasion. Results Cx43 was significantly downregulated in GC tissues and cell lines, while miR-301-3p expression was negatively correlated with Cx43 mRNA levels. The expression levels of Cx43 and miR-301-3p were closely associated with the differentiation, TNM stage, vascular invasion, and lymph node metastasis status of GC patients. Cx43 overexpression could suppress the proliferation, migration, and invasion of GC cells. Cx43 mRNA is a direct target of miR-301-3p, and transfection of an miR-301-3p mimic could reverse the inhibitory effects of Cx43. Conclusion The miR-301-3p- Cx43 axis is involved in the development and progression of GC by affecting the proliferation, migration, and invasion of GC cells.

scholarly journals KK-LC-1 may be an effective prognostic biomarker for gastric cancer

2020 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Staining Intensity ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

High-Expression HBO1 Predicts Poor Prognosis in Gastric Cancer

2019 ◽  
Vol 152 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Yan Wang ◽  
Sufang Chen ◽  
Wei Tian ◽  
Qing Zhang ◽  
Chunyi Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Messenger Rna ◽  
Origin Recognition Complex ◽  
Tnm Staging ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Serum Carcinoembryonic Antigen ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
Kaplan Meier Plotter

Abstract Objectives Our goal was to assess the expression of histone acetyltransferase binding to origin recognition complex 1 (HBO1) in gastric cancer and the effect on prognosis for the patients. Methods We used quantitative reverse transcription polymerase chain reaction, Western blot, and tissue microarray immunohistochemistry to investigate the expressions of HBO1 messenger RNA (mRNA) and protein in gastric cancer tissues. Online resources, including Oncomine and Kaplan-Meier Plotter, were used to further assess the correlation between HBO1 expression and the prognosis of the patients with gastric cancer. Results HBO1 mRNA and protein expressions in gastric cancer tissues were both significantly higher than those in normal tissues. The correlations between high HBO1 expression and differentiation, invasive depth (T), lymph node metastasis (N), distant metastasis (M), TNM staging, and serum carcinoembryonic antigen levels were positive. High HBO1 expression was negatively correlated with survival time in patients with gastric cancer. Conclusions HBO1 might be a valuable biomarker to evaluate the prognosis of patients with gastric cancer.

scholarly journals Identification of Key Genes in Gastric Cancer by Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xinyu Chong ◽  
Rui Peng ◽  
Yan Sun ◽  
Luyu Zhang ◽  
Zheng Zhang
Keyword(s):  
Gastric Cancer ◽  
Topological Analysis ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Key Genes ◽  
Secreted Phosphoprotein 1 ◽  
Centrality Analysis

Gastric cancer (GC) is one of the most common malignancies of the digestive system with few genetic markers for its early detection and prevention. In this study, differentially expressed genes (DEGs) were analyzed using GEO2R from GSE54129 and GSE13911 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING, and Cytoscape. Finally, we performed survival analysis of key genes through the Kaplan-Meier plotter. A total of 1034 DEGs were identified in GC. GO and KEGG results showed that DEGs mainly enriched in plasma membrane, cell adhesion, and PI3K-Akt signaling pathway. Subsequently, the PPI network with 44 nodes and 333 edges was constructed, and 18 candidate genes in the network were focused on by centrality analysis and module analysis. Furthermore, data showed that high expressions of fibronectin 1(FN1), the tissue inhibitor of metalloproteinases 1 (TIMP1), secreted phosphoprotein 1 (SPP1), apolipoprotein E (APOE), and versican (VCAN) were related to poor overall survivals in GC patients. In summary, this study suggests that FN1, TIMP1, SPP1, APOE, and VCAN may act as the key genes in GC.

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