Identification by Bioinformatics Analysis of Potential Key Genes Related to the Progression and Prognosis of Gastric Cancer

Gao, Wencang; Yang, Min

doi:10.3389/fonc.2022.881015

Cited by 5 publications

(10 citation statements)

References 27 publications

(26 reference statements)

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“…Besides these, Xie et al (2015) established a multi-index prediction model based on the six kinds of biomarkers (CEA, CA199, H.P., P53, PG Ⅰ, and PG Ⅱ), which was designed to achieve early screening and therapeutic evaluation of GC patients. However, the above biomarkers and therapeutic targets had insufficient specificity in the early diagnosis of GC and could not accurately evaluate tumor progression and survival time (Gao and Yang, 2022). In this study, COL1A2, TIMP1, THY1, and BGN were identified as significant DEGs for both the GC with ES and the GC with LS.…”

Section: Pouyssegurmentioning

confidence: 76%

Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages

Liang²,

Tu³

et al. 2022

Front. Genet.

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Background: Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods.Methods: Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups’ differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein–protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database.Results: After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes.Conclusion: The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.

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Section: Pouyssegurmentioning

confidence: 76%

Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages

Liang²,

Tu³

et al. 2022

Front. Genet.

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“…Previous studies have reported that AGT was associated with poor prognosis in GC [ 25 , 30 ]. To investigate the functions of AGT in GC, we knocked down the expression of AGT in HGC-27 and BGC-823 cells via LV-Sh-AGT.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, AGT has been reported to be associated with poor prognosis and occurrence in GC [ 25 ]. Targeting AGT has been widely used to suppress tumor proliferation, migration, and invasion [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, previous studies have found that AGT was correlated with GC progression and serves as a prognostic biomarker [ 25 , 62 ]. Our findings solidify these analyses and unravel the function of AGT in the chemotherapy response of GC patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, AGT, which is attributed to tumor proliferation and migration, as well as invasion, has been demonstrated to be a diagnostic and prognostic biomarker in colorectal carcinoma [ 24 ]. In GC, the use of AGT as a prognostic molecule has been issued in previous studies [ 25 ]. However, the function of AGT in chemotherapy and the underlying mechanism of AGT are poorly understood in the context of GC.…”

Section: Introductionmentioning

confidence: 99%

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System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy

Zhu

Zhang

et al. 2023

Pharmaceutics

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Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide, and chemotherapy is still a standard strategy for treating patients with advanced GC. Lipid metabolism has been reported to play an important role in the carcinogenesis and development of GC. However, the potential values of lipid-metabolism-related genes (LMRGs) concerning prognostic value and the prediction of chemotherapy responsiveness in GC remains unclear. A total of 714 stomach adenocarcinoma patients were enrolled from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Using univariate Cox and LASSO regression analyses, we developed a risk signature based on LMRGs that can distinguish high-GC-risk patients from low-risk patients with significant differences in overall survival. We further validated this signature prognostic value using the GEO database. The R package “pRRophetic” was applied to calculate the sensitivity of each sample from high- and low-risk groups to chemotherapy drugs. The expression of two LMRGs, AGT and ENPP7, can predict the prognosis and response to chemotherapy in GC. Furthermore, AGT significantly promoted GC growth and migration, and the downregulation of AGT enhanced the chemotherapy response of GC both in vitro and in vivo. Mechanistically, AGT induced significant levels of epithelial–mesenchymal transition (EMT) through the PI3K/AKT pathway. The PI3K/AKT pathway agonist 740 Y-P can restore the EMT of GC cells impaired by AGT knockdown and treatment with 5-fluorouracil. Our findings suggest that AGT plays a key role in the development of GC, and targeting AGT may help to improve the chemotherapy response of GC patients.

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