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Published on: July 22, 2020
Revealing potential immunotherapy targets through analysis of a ceRNA network in human colon adenocarcinoma
Changhao Li1, Zhenyu Zhu1, Qingsheng Hou1
1Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Background:
Microsatellite instability-high (MSI-H) is a special type of human colon adenocarcinoma (COAD) that responds well to immunotherapy. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are important members of competing endogenous RNAs (ceRNAs) networks, are involved in the tumorigenesis and development of MSI-H COAD. This study aimed to establish a ceRNA network for MSI in COAD to identify targets and prognostic markers that may explain the effects of immunotherapy.
Methods:
COAD sequencing data were extracted from The Cancer Genome Atlas (TCGA), after which differentially expressed miRNAs, lncRNAs, and mRNAs were determined according to microsatellite status. After building a network based on the ceRNA hypothesis, the relationships between microsatellite status and clinical features were explored. Biological processes in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were analyzed for specific miRNAs, lncRNAs, and mRNAs. Survival analysis was used to identify potential biomarkers.
Results:
Based on the inclusion criteria, a total of 363 COAD samples were obtained from TCGA. Strict screening criteria were used to identify differentially expressed RNAs in the MSI-H and microsatellite-stable groups, with 82 miRNAs, 1,280 lncRNAs, and 2121 mRNAs obtained (fold change >2, false discovery rate <0.01). Based on the RNA interaction mechanism, a miRNA-lncRNA-mRNA network was constructed, through which a subnetwork composed of 5 miRNAs was discovered. hsa-miR-31-5p, hsa-miR-302a-3p, hsa-miR-302b-3p, hsa-miR-302d-3p, hsa-miR-3619-5p and the RNAs interaction with them have the potential to become novel targets to change the effect of existing immunotherapy. GO and KEGG analyses showed that these differentially expressed miRNAs, lncRNAs, and mRNAs may play key roles in tumorigenesis, tumor development, and drug efficacy, with natural killer cells potentially becoming the next emerging targets for immunotherapy enhancement. Moreover, survival analysis identified 10 lncRNAs as potential survival markers.
Conclusions:
This study identified novel immunotherapy targets and revealed potential biomarkers for COAD according to microsatellite status.
Insights
This study identifies novel immunotherapy targets for microsatellite instability-high colon adenocarcinoma (MSI-H COAD) by analyzing RNA interactions. It reveals potential biomarkers and therapeutic strategies to enhance immunotherapy effectiveness.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Microsatellite instability-high (MSI-H) colon adenocarcinoma (COAD) shows a strong response to immunotherapy.
- MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are key players in competing endogenous RNA (ceRNA) networks, influencing MSI-H COAD development.
Purpose of the Study:
- To establish a ceRNA network for MSI in COAD.
- To identify novel immunotherapy targets and prognostic markers in MSI-H COAD.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) COAD sequencing data.
- Identified differentially expressed miRNAs, lncRNAs, and mRNAs based on microsatellite status.
- Constructed a miRNA-lncRNA-mRNA ceRNA network and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Conducted survival analysis to identify potential biomarkers.
Main Results:
- A ceRNA network was constructed, revealing a subnetwork of 5 miRNAs (hsa-miR-31-5p, hsa-miR-302a-3p, hsa-miR-302b-3p, hsa-miR-302d-3p, hsa-miR-3619-5p) with potential as immunotherapy targets.
- Identified differentially expressed RNAs involved in tumorigenesis, tumor development, and drug efficacy.
- Natural killer cells emerged as potential targets for immunotherapy enhancement.
- Discovered 10 lncRNAs as potential survival markers for COAD.
Conclusions:
- Identified novel immunotherapy targets for COAD based on microsatellite status.
- Revealed potential biomarkers for predicting prognosis and guiding immunotherapy in COAD.
