Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Wang, Qing; Liang, Jiahong; Hu, Xianyu; Gu, Shen; Xu, Qingdong; Jiang, Yan

doi:10.1042/bsr20210055

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…Other studies also illustrated a prognostic model for GC patients. Wang et al 8 revealed that early B cell factors are prognostic biomarkers for GC patients, and 5-fluorouracil, methotrexate, and vorinostat are suitable to inhibit the function of early B cell factors and suppress the process of tumorigenesis. Li et al 9 developed a prognostic model, IDOScore, based on the expression levels of TAP2, SERPINB5, LTBP1 and LAMC1.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis

Wang¹,

Wang²,

Hu³

et al. 2021

IJGM

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Background: Gastric cancer (GC) is the third most frequent malignant tumour in the Chinese population, let alone the whole world. Recently, most prognostic models have only focused on the levels of several genes, miRNAs, lncRNAs, gene mutations, or DNA methylation; however, the activation status of biological pathways is more stable and can reflect the comprehensive inner conditions of tumours. Methods: We collected samples from the Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort and GSE62254 cohort, with a total of 594 patients. We employed GSEA to first compare the diverse activated signalling pathways between dead GC patients and living patients. The least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently performed by the "glmnet" package to generate a prognostic signature.Results: We extracted a total of 218 genes from the KEGG Focal Adhesion and KEGG ECM Receptor Interaction pathways, which showed significant activation in dead GC patients in two enrolled cohorts, for subsequent LASSO analysis. In the TCGA-STAD cohort, patients in the high-risk group faced a significantly poorer prognosis than those in the low-risk group (P < 0.001, HR: 4.62, 95% CI: 3.447-6.183), with an AUC of 0.694. In the GSE62254 cohort, the HR value was 4.94 (95% CI: 3.413-7.165), and the AUC value was as high as 0.834. A high-risk score and poor prognosis correlated with infiltrated dendritic cells, and the receptor of IFN-α was also positively linked with the risk score, as well as poor prognosis. GC patients with high-risk scores were more likely to respond to CTLA4 treatment but not PD1 treatment. Conclusion: Taken together, we established and verified an extracellular matrix prognostic model of gastric cancer patients. The model can be used to evaluate the risk of death of GC patients, as well as the response to anti-CTLA4 immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis

Wang¹,

Wang²,

Hu³

et al. 2021

IJGM

Self Cite

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Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma

Chang

et al. 2023

J Transl Med

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Background The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer. Methods In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related risk model based on available TCGA and GEO databases. The tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, and drug sensitivity of gastric adenocarcinoma patients were also investigated using R language, GraphPad Prism 8 and online databases. Results We established a mitochondrial-related risk prognostic model including NOX4, ALDH3A2, FKBP10 and MAOA and validated its predictive power. This risk model indicated that the immune cell infiltration in high-risk group was significantly different from that in the low-risk group. Besides, the risk score was closely related to TME signature genes and immune checkpoint molecules, suggesting that the immunosuppressive tumor microenvironment might lead to poor prognosis in high-risk groups. Moreover, TIDE analysis demonstrated that combined analysis of risk score and immune score, or stromal score, or microsatellite status could more effectively predict the benefit of immunotherapy in STAD patients with different stratifications. Finally, rapamycin, PD-0325901 and dasatinib were found to be more effective for patients in the high-risk group, whereas AZD7762, CEP-701 and methotrexate were predicted to be more effective for patients in the low-risk group. Conclusions Our results suggest that the mitochondrial-related risk model could be a reliable prognostic biomarker for personalized treatment of STAD patients.

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Early growth response 1 transcription factor is essential for the pathogenic properties of human endometriotic epithelial cells

et al. 2022

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Although a benign gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion, and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side-effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the pathogenic properties of endometriotic cells. Genome-wide transcriptomics identified an EGR1-dependent transcriptome in human endometriotic epithelial cells that potentially encodes a diverse spectrum of proteins that are known to be involved in tissue pathologies. To underscore the utility of this transcriptomic dataset, we demonstrate that carbonic anhydrase IX (CAIX), a homeostatic regulator of intracellular pH, is not only a molecular target of EGR1 but is important for maintaining many of the cellular properties of human endometriotic epithelial cells that are also ascribed to EGR1. Considering therapeutic intervention strategies are actively being developed for EGR1 and CAIX in the treatment of other pathologies, we believe EGR1 and its transcriptome (which includes CAIX) will offer not only a new conceptual framework to advance our understanding of endometriosis but will furnish new molecular vulnerabilities to be leveraged as potential therapeutic options in the future treatment of endometriosis.

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Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Cited by 3 publications

References 58 publications

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis

Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma

Early growth response 1 transcription factor is essential for the pathogenic properties of human endometriotic epithelial cells

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