scholarly journals Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

Author(s):  
Deli Mao ◽  
Rui Xu ◽  
Hengxing Chen ◽  
Xiancong Chen ◽  
Dongsheng Li ◽  
...  

Background: Focal adhesion, as the intermediary between tumor cells and extracellular matrix communication, plays a variety of roles in tumor invasion, migration, and drug resistance. However, the potential role of focal adhesion-related genes in the microenvironment, immune cell infiltration, and drug sensitivity of gastric cancer (GC) has not yet been revealed.Methods: The genetic and transcriptional perspectives of focal adhesion-related genes were systematically analyzed. From a genetic perspective, the focal adhesion index (FAI) was constructed based on 18 prognosis-related focus adhesion-related genes to evaluate the immune microenvironment and drug sensitivity. Then three prognosis-related genes were used for consistent clustering to identify GC subtypes. Finally, use FLT1, EGF, COL5A2, and M2 macrophages to develop risk signatures, and establish a nomogram together with clinicopathological characteristics.Results: Mutations in the focal adhesion-related gene affect the survival time and clinical characteristics of GC patients. FAI has been associated with a shorter survival time, immune signaling pathways, M2 macrophage infiltration, epithelial-mesenchymal transition (EMT) signaling, and diffuse type of GC. FAI recognizes ALK, cell cycle, and BMX signaling pathways inhibitors as sensitive agents for the treatment of GC. FLT1, EGF, and COL5A2 may distinguish GC subtypes. The established risk signature is of great significance to the prognostic evaluation of GC based on FLT1, EGF, and COL5A2 and M2 macrophage expression.Conclusion: The focal adhesion-related gene is a potential biomarker for the evaluation of the immune microenvironment and prognosis. This work emphasizes the potential impact of the focal adhesion pathway in GC therapy and highlights its guiding role in prognostic evaluation.

2020 ◽  
Vol 29 ◽  
pp. 096368972097713
Author(s):  
Xueping Jiang ◽  
Yanping Gao ◽  
Nannan Zhang ◽  
Cheng Yuan ◽  
Yuan Luo ◽  
...  

Tumor microenvironment (TME) has critical impacts on the pathogenesis of lung adenocarcinoma (LUAD). However, the molecular mechanism of TME effects on the prognosis of LUAD patients remains unclear. Our study aimed to establish an immune-related gene pair (IRGP) model for prognosis prediction and internal mechanism investigation. Based on 702 TME-related differentially expressed genes (DEGs) extracted from The Cancer Genome Atlas (TCGA) training cohort using the ESTIMATE algorithm, a 10-IRGP signature was established to predict LUAD patient prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that DEGs were significantly associated with tumor immune response. In both TCGA training and Gene Expression Omnibus validation datasets, the risk score was an independent prognostic factor for LUAD patients using Lasso-Cox analysis, and patients in the high-risk group had poorer prognosis than those in the low-risk one. In the high-risk group, M2 macrophage and neutrophil infiltrations were higher, while the levels of T cell follicular helpers were significantly lower. The gene set enrichment analysis results showed that DNA repair signaling pathways were involved. In summary, we established an IRGP signature as a potential biomarker to predict the prognosis of LUAD patients.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 66-66
Author(s):  
Koung Jin Suh ◽  
Jin Won Kim ◽  
Ji Eun Kim ◽  
Jiwon Koh ◽  
Ji-Won Kim ◽  
...  

66 Background: Peripheral regulatory T cells (pTregs) might involve in tumor immune microenvironment. We aim to evaluate the correlation between pTregs and tumor immune microenvironment. Methods: pTregs status was determined from assessment of the pTreg/total T cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation) through epigenetic pattern of bisulfite pyrosequencing in long-term stored peripheral blood of 442 gastric cancer patients who received curative surgery. Immunohistochemical staining of multiple immune-related markers including CD3, CD4, CD8, Foxp3, 1-selectin arginase, ADAM metallopeptidase domain 17, CD163 and CD45RO within tumor microenvironment were performed in resected gastric tumor specimen. Results: The median value of FoxP3-TSDR and CD3G/CD3D demethylation was 5.8% and 32.3%, respectively. When pTreg/total T cell ratio was divided into eight equal groups from the lowest to the highest value, the extreme pTreg/total T cell ratio of the upper eighth and the lower eighth was significantly associated with lower CD45RO expressed cell counts within tumor microenvironment. In terms of arginase and CD163, inverse results were observed. Patients with extreme pTreg/total T cell ratio had significantly shorter disease-free survival (DFS) and overall survival (OS) compared to the patients with non-extreme pTreg/total T cell ratio. Multivariate analysis which included age, stage, lymphatic invasion, vascular invasion, and perineural invasion as covariates demonstrated that the extreme pTreg/total T cell ratio was an independent predictor for shorter DFS (HR 1.740, 95% CI 1.128 – 2.682; p = 0.012) and OS (HR 1.900, 95% CI 1.175 – 3.070; p = 0.003). Conclusions: Our results suggest that the pTreg/total T cell ratio determined by epigenetic methylation analysis is correlated with specific immune cell infiltration within tumor microenvironment in resected gastric tumors, and gives prognostic information in gastric cancer patients. pTreg/total T cell ratio could be an easy-obtained potential biomarker for prognosis and future immunotherapeutic treatment strategies.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 111-OR
Author(s):  
GIORGIO BASILE ◽  
AMEDEO VETERE ◽  
KA-CHEUK LIU ◽  
JIANG HU ◽  
OLOV ANDERSSON ◽  
...  

2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.


2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi

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.


2013 ◽  
Vol 17 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Hiroyuki Naitoh ◽  
Hiroshi Yamamoto ◽  
Satoshi Murata ◽  
Hisayuki Kobayashi ◽  
Katsunori Inoue ◽  
...  

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