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Updated: Apr 15, 2026
A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Identification of dysfunctional biological pathways and their synergistic mechanism in hepatocellular carcinoma
Jun Liang1, Jing Lv1, Zimin Liu1
1Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Background:
Hepatocellular carcinoma (HCC) is a lethal and prevalent cancer worldwide. This study was conducted to investigate dysfunctional pathways and their synergistic mechanism in the HCC process.
Methods:
We downloaded transcriptome profiling data (GSE25097) from the Gene Expression Omnibus (GEO) database, including 6 healthy liver samples, 40 cirrhosis samples, 243 adjacent non-tumor samples, and 268 HCC samples. Robust Multi-Array (RMA) in R software was employed to preprocess the downloaded dataset, and Student's t-test (FDR less than 0.001) was performed to identify the differentially expressed genes (DEGs) between 4 sample groups. Then, pathway enrichment analysis (FDR less than 0.05) based on iSubpathwayMiner was performed. Furthermore, we performed collaborative analysis on these pathways through calculating the Jaccard index, and crosstalk networks were constructed and visualized by Cytoscape.
Results:
Totally, 4617, 9517, and 12,479 DEGs were identified between healthy liver and cirrhosis samples, cirrhosis and adjacent non-tumor samples, and adjacent non-tumor and HCC samples, respectively. Furthermore, a total of 26 crosstalks involving 13 pathways, 78 crosstalks involving 54 pathways, and 86 crosstalks involving 52 pathways were identified through the DEGs between healthy liver and cirrhosis samples, cirrhosis and adjacent non-tumor samples, and adjacent non-tumor and HCC samples, respectively. Moreover, 5 dysfunctional pathways were found to co-exist in the three processes of HCC. Among them, 3 dysfunctional pathways have collaborative relationship, including Staphylococcus aureus infection, leishmaniasis, and Chagas disease.
Conclusions:
In this study, dysfunctional pathways in the HCC process and crosstalks between these pathways were investigated for the first time, providing new insight into the potential mechanisms of HCC.
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