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Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer
Shuai Xue1, Ming Ma2, Songhua Bei1
1Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China.
Abstract:
Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan-Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.
Insights
This study identifies 11 immunoregulatory factors predicting gastric cancer prognosis. CXCR4 is a key factor linked to poor survival and promotes cancer progression, offering potential diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint blockade is a key cancer therapy.
- Gastric cancer (GC) prognosis requires better predictive models.
- Immunoregulatory factors play a role in tumor progression.
Purpose of the Study:
- To establish a prognostic model for gastric cancer using immunoregulatory factor gene expression.
- To identify key immunomodulatory factors associated with GC patient survival.
- To investigate the role of CXCR4 in GC progression.
Main Methods:
- Utilized TCGA database to identify 234 differentially expressed immunoregulatory factors.
- Performed Gene Ontology (GO) and KEGG pathway enrichment analysis.
- Employed Cox regression and Kaplan-Meier analyses to assess prognostic significance.
Main Results:
- Identified 11 immunoregulatory factors significantly correlated with GC overall survival.
- CXCR4 expression was linked to poor prognosis, advanced stage, and grade in GC.
- CXCR4 promoted GC cell proliferation, migration, and invasion in vitro.
Conclusions:
- 11 immunomodulatory factors have prognostic value in gastric cancer.
- CXCR4 serves as an independent prognostic indicator for GC patients.
- Findings may improve individualized GC prognosis and guide diagnosis/treatment.
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