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pmid:34527669
HCG18 Participates in Vascular Invasion of Hepatocellular Carcinoma by Regulating Macrophages and Tumor Stem Cells.
Liwei Zhang · Zhiwei Wang · Mingxing Li · Peng Sun · Tao Bai · Wang Wang · Hualong Bai · Jianjun Gou · Zhiju Wang
Frontiers in cell and developmental biology · 2021 doi:10.3389/fcell.2021.707073
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Experiment
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Complete file
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The key regulatory networks, transcription factors and core genes related to vascular invasion and prognosis were explored based on the CE mechanism. Survival analysis and gene set enrichment were used to explore pathways related to vascular invasion. Combined with single-cell transcriptome data, the distribution of core gene expression in various cells was observed. Cellular communication analysis was used to identify key cells associated with vascular invasion. Pseudo-temporal locus analysis was used to explore the regulation of core genes in key cell phenotypes. The influence of core genes on current immune checkpoint therapy was evaluated and correlations with tumor stem cell scores were explored.\nRESULTS: We obtained a network containing 1,249 pairs of CE regulatory relationships, including 579 differential proteins, 28 non-coding RNAs, and 37 miRNAs. Three key transcription factors, ILF2, YBX1, and HMGA1, were identified, all regulated by HCG18 lncRNA. ScRNAseq showed that HCG18 co-localized with macrophages and stem cells. CIBERSORTx assessed 22 types of immune cells in HCC and found that HCG18 was positively correlated with M0 macrophages, while being negatively correlated with M1 and M2 macrophages, monocytes, and dendritic cells. Cluster analysis based on patient prognosis suggested that regulating phenotypic transformation of macrophages could be an effective intervention for treating HCC. At the same time, higher expression of HCG18, HMGA1, ILF2, and YBX1 was associated with a higher stem cell score and less tumor differentiation. Pan cancer analysis indicated that high expression of HCG18 implies high sensitivity to immune checkpoint therapy.\nCONCLUSION: HCG18 participates in vascular invasion of HCC by regulating macrophages and tumor stem cells through three key transcription factors, YBX1, ILF2, and HMGA1.", "claims": [{"id": "claim-method", "statement": "To this end, we performed a multivariate Cox survival analysis of clinical information recorded in samples from the TCGA database (Figure 1A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34527669", "locator": "sections[13] \"Vascular Invasion of Hepatocellular Carcinoma Has Independent Prognostic Significance\" paragraph 2", "quote": "To this end, we performed a multivariate Cox survival analysis of clinical information recorded in samples from the TCGA database (Figure 1A)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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