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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer
Jie Chen1, Jing Gui Chen1, Bo Sun1
1Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Abstract:
This study aimed to identify significant immune microenvironment-related competing endogenous RNA (CeRNA) regulatory axis in gastric cancer (GC). Analysis of differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was performed for the microarray datasets. After abundance analysis of immune cell's infiltration, immune-related mRNAs and lncRNAs were obtained. Meanwhile, according to the Pearson correlation coefficient between immune-related mRNAs and lncRNAs, the co-expression mRNA-lncRNA pairs were screened. Furthermore, the target genes of co-existance miRNAs were predicted, and miRNA-lncRNA pairs were identified. Finally, the lncRNA-miRNA and miRNA-mRNA relationship regulated by the same miRNA was screened. Combining with the co-expression relationship between lncRNA and mRNA, the CeRNA network was constructed. In abundance analysis of immune cell's infiltration, a total of eight immune cells were obtained, in addition, 83 immune-related DElncRNAs and 705 immune-related DEmRNAs were screened. KEGG pathway enrichment analysis showed that these mRNAs were mainly involved in PI3K-Akt signaling pathway and human papillomavirus infection, while lncRNA were relevant to gastric acid secretion. A total of 25 miRNAs were significantly associated with immune-related mRNAs, such as hsa-miR-148a-3p, hsa-miR-17-5p, and hsa-miR-25-3p. From the mRNA-miRNA-lncRNA CeRNA network, we observed that AC104389.28─miR-17-5─SMAD5 axis and LINC01133─miR-17-5p─PBLD axis played a crucial role in the development of GC. Furthermore, resting memory CD4 T cells and plasma cells were closely associated with the pathogenesis of GC, and these immune cells might be affected by the key genes. The present study identified key genes that associated with immune microenvironment in GC, providing potential molecular targets for immunotherapy of GC.
Insights
This study identifies key competing endogenous RNA (CeRNA) networks in gastric cancer (GC) by analyzing immune cell infiltration and gene expression. These findings reveal potential molecular targets for GC immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Gastric cancer (GC) pathogenesis involves complex interactions within the tumor immune microenvironment.
- Competing endogenous RNA (CeRNA) networks, involving long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), are increasingly recognized for their role in cancer development.
- Identifying specific CeRNA regulatory axes linked to immune cells in GC is crucial for understanding disease progression and developing novel therapies.
Purpose of the Study:
- To identify significant immune microenvironment-related CeRNA regulatory axes in gastric cancer (GC).
- To explore the relationship between immune cell infiltration and gene expression patterns in GC.
- To uncover potential molecular targets for GC immunotherapy based on CeRNA networks.
Main Methods:
- Analysis of differentially expressed mRNAs, miRNAs, and lncRNAs from microarray datasets.
- Immune cell infiltration abundance analysis to identify immune-related genes.
- Construction of an mRNA-miRNA-lncRNA CeRNA network using Pearson correlation and target prediction.
- KEGG pathway enrichment analysis to understand the functional roles of identified genes.
Main Results:
- Identification of 83 immune-related DElncRNAs and 705 immune-related DEmRNAs.
- KEGG analysis revealed involvement of PI3K-Akt signaling pathway and human papillomavirus infection for mRNAs, and gastric acid secretion for lncRNAs.
- The AC104389.28─miR-17-5─SMAD5 and LINC01133─miR-17-5p─PBLD axes were identified as crucial in GC development.
- Resting memory CD4 T cells and plasma cells were significantly associated with GC pathogenesis.
Conclusions:
- The study successfully constructed a GC immune microenvironment-related CeRNA network.
- Key regulatory axes like AC104389.28─miR-17-5─SMAD5 and LINC01133─miR-17-5p─PBLD were identified as critical players in GC.
- These findings provide potential molecular targets for GC immunotherapy, particularly by targeting identified immune cells and key genes.
