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Study on miRNAs in Pan-Cancer of the Digestive Tract Based on the Illumina HiSeq System Data Sequencing
Chun-Hui Lai1, Xu-Zhi Liang2, Xiu-Yun Liang1
1Department of Clinical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/Nanning Second People's Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
Objective:
miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ).
Materials And Methods:
After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs' target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan-Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development.
Results:
Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway.
Conclusion:
The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.
Insights
This study identified key microRNAs (miRNAs) and their target genes in digestive tract cancers. These findings offer new directions for diagnosing and treating esophageal, gastric, colon, and rectal adenocarcinomas.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are increasingly recognized as critical regulators in cancer development and progression.
- Digestive tract cancers, including esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ), represent a significant global health burden.
- Identifying specific miRNAs and their target genes is crucial for understanding cancer biology and developing targeted therapies.
Purpose of the Study:
- To investigate the biological functions of key miRNAs and their target genes in four major digestive tract cancers.
- To identify differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in ESCA, GAC, COAD, and READ.
- To explore the diagnostic and prognostic value of identified miRNAs in these malignancies.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database to screen DEMIs and DEMs in digestive cancers.
- Employed miRWalk 2.0 for miRNA target gene prediction and constructed miRNA-mRNA regulatory networks.
- Applied univariate Cox regression, Kaplan-Meier analysis, and bioinformatics tools (PPI, GO, KEGG, GCBI) for prognostic and functional analysis.
Main Results:
- Identified 3 DEMIs (miR-7-3, miR-328, miR-323a) with significant prognostic value.
- Discovered 3 DEMIs (miR-490-3p, miR-133a-3p, miR-552-3p) with high diagnostic value in READ and moderate value in ESCA, GAC, and COAD.
- Established a miRNA-mRNA regulatory network involving 3 DEMIs and 281 target genes, primarily linked to cell proliferation, migration, and the PI3K-Akt pathway.
Conclusions:
- Significant DEMIs with diagnostic and prognostic value in digestive tract cancers were identified.
- These findings highlight potential novel biomarkers for diagnosis and prognosis.
- The study provides a foundation for developing targeted therapeutic strategies for digestive tract cancers.
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