Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.716461
Keywords
gastric cancer; focal adhesion; immune microenvironment; prognostic signature; biomarker
Categories
Funding
- National Natural Science Foundation of China [82073148]
- Sanming Project of Medicine in Shenzhen [SZSM201911010]
- Shenzhen Key Medical Discipline Construction Fund [SZXK016]
- Guangdong Provincial Key Laboratory of Digestive Cancer Research [2021B1212040006]
- Shenzhen Sustainable Project [KCXFZ202002011010593, ZSQYJZPI202001]
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This study systematically analyzed the role of focal adhesion-related genes in gastric cancer and found that mutations in these genes can affect patients' survival time and clinical characteristics. The research also indicated that the focal adhesion index is associated with the immune microenvironment, M2 macrophage infiltration, and GC subtypes, providing important insights for prognostic evaluation of gastric cancer.
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.
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