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Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation
Chao Song1, Wenbo Liu1, Xiaoyu Wang2
1The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Introduction:
Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.
Methods:
Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.
Results:
Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.
Conclusion:
The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.
Insights
Anoikis, a cell death process, is crucial in gastric cancer metastasis. This study identified three gastric cancer subtypes based on anoikis genes and validated CYP1B1 as a promoter of tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Distant metastasis significantly impacts gastric cancer prognosis.
- Anoikis, or anchorage-independent cell death, is implicated in gastric cancer metastasis.
Purpose of the Study:
- To classify gastric cancer subtypes based on anoikis gene expression.
- To identify prognostic anoikis genes and their role in gastric cancer progression.
- To investigate the function of differentially expressed anoikis genes in gastric cancer.
Main Methods:
- Downloaded and analyzed TCGA-STAD dataset and anoikis gene sets.
- Performed consensus clustering, WGCNA, and differential gene expression analysis.
- Conducted COX survival analysis, nomogram construction, and in vitro/in vivo validation of CYP1B1.
Main Results:
- Identified three distinct gastric cancer subtypes with varying expression profiles, pathways, and immune infiltration.
- Discovered significant differences in immune cell abundance (NK cells, B cells, M2 macrophages) among subtypes.
- Validated CYP1B1 as a highly expressed gene in gastric cancer that promotes cell invasion, migration, and tumor progression by resisting anoikis.
Conclusions:
- Gastric cancer subtypes exhibit diverse expression patterns of anoikis-related genes.
- Findings support the development of personalized treatment strategies for gastric cancer based on anoikis gene expression.
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