scholarly journals Bioinformatic analysis suggests that UGT2B15 activates the Hippo‑YAP signaling pathway leading to the pathogenesis of gastric cancer

2018 ◽  
Author(s):  
Xuanmin Chen ◽  
Defeng Li ◽  
Nannan Wang ◽  
Meifeng Yang ◽  
Aijun Liao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Bioinformatic Analysis

scholarly journals Identification of INHBA as a Potential Biomarker for Gastric Cancer by Comprehensive Analysis

2021 ◽  
Author(s):  
Guangjie Liu ◽  
Xiao-jie Hu ◽  
Yuxuan Jia ◽  
Bing-jie Huo ◽  
Cheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Tgf Beta ◽  
Normal Tissues ◽  
Potential Biomarker

Abstract Inhibin subunit beta A (INHBA) is a member of the TGF-beta (transforming growth factor-beta) superfamily proteins, which plays a fundamental role in various cancers. However, little is known about the exact role of INHBA in patients with gastric cancer (GC). The present study aims to explore the relationship between INHBA and GC and detect the underlying mechanisms. Multiple bioinformatic approaches were first preformed basing on TIMER, GEPIA2, GEO, Oncomine and UALCAN databases, which revealed that INHBA was highly elevated in GC. This result was proved by Immunohistochemistry (IHC) and real time polymerase chain reaction (RT-PCR) in 65 cases of GC tissues in our study. The bioinformatic analysis also revealed that high expression of INHBA was significantly related to unfavorable prognosis of GC. To detect the underlying mechanism, further analysis was performed basing on Kaplan Meier plotter database and found that poor prognosis of GC was related to infiltration of different enriched immune-cell subgroups. That was INHBA being negatively correlated with B cell while positively correlated with CD8 + T cells, macrophage, neutrophil and dendritic cell infiltration. However, there was week significant methylation level change between tumor and normal tissues. Moreover, INHBA mainly enriched on cancer-related signaling pathways, including TGF-beta signaling pathway, ECM-receptor signaling pathway, PID ALK1/2 pathway, and AGE-RAGE signaling pathway, which provide a new insight for future in-depth study.

Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Tumor Immunology ◽  
Bioinformatics Analysis ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

scholarly journals Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ben Liu ◽  
Meng Zhou ◽  
Xiangchun Li ◽  
Xining Zhang ◽  
Qinghua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gender Bias ◽  
Gender Disparity ◽  
Gene Set Enrichment Analysis ◽  
Cancer Type ◽  
Female Patients

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.

The PI3K/Akt/mTOR signaling pathway in gastric cancer; from oncogenic variations to the possibilities for pharmacologic interventions

2021 ◽  
pp. 173983
Author(s):  
Ayda Baghery Saghchy Khorasani ◽  
Atieh Pourbagheri-Sigaroodi ◽  
Ali Pirsalehi ◽  
Ava Safaroghli-azar ◽  
Mohammad Reza Zali ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Immune Cell ◽  
System Development ◽  
Wnt Signaling Pathway ◽  
Immune System Development ◽  
Precision Therapy ◽  
Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

STAM2 knockdown inhibits proliferation, migration, and invasion by affecting the JAK2/STAT3 signaling pathway in gastric cancer

2021 ◽  
Author(s):  
Yang Yang ◽  
Q i Zhang ◽  
Jiakui Liang ◽  
Meiyuan Yang ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Mammalian Cells ◽  
Migration And Invasion ◽  
Boyden Chamber ◽  
Pathway Enrichment Analysis ◽  
Stat3 Signaling ◽  
Advanced Tumor ◽  
Stat3 Signaling Pathway ◽  
Tumor Node Metastasis Stage

Abstract Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which regulates receptor signaling and trafficking of mammalian cells. However, its role in gastric cancer (GC) remains undiscovered. In this study, we aimed to investigate the functions of STAM2 in GC. The mRNA and protein expression levels of STAM2 were measured by quantitative real-time PCR, western blot analysis, and immunohistochemistry. STAM2 was stably silenced in AGS and HGC-27 cells using small interfering RNA. The function of STAM2 in GC cells was further investigated by CCK-8 assay, EdU incorporation assay, flow cytometry, and scratch wound healing and Boyden chamber assays. Additionally, we conducted biological pathway enrichment analysis and rescue assays to explore the effects of STAM2 on JAK/STAT signaling pathway. Our results showed that STAM2 is remarkably highly expressed in GC tissues and cells, and overexpressed STAM2 is correlated with tumor size, advanced tumor node metastasis stage, and poor prognosis. In addition, STAM2 knockdown could significantly inhibit proliferation, block cell cycle, and restrain migration and invasion capabilities of GC cells. Mechanistically, we found that STAM2 knockdown effectively decreased the expressions of MMP2 and MMP9 and the phosphorylation levels of JAK2 and STAT3. Taken together, this study revealed that STAM2 knockdown could suppress malignant process by targeting the JAK2/STAT3 signaling pathway in GC.

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