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  • Title: A prognostic exosome-related long non-coding RNAs risk model related to the immune microenvironment and therapeutic responses for patients with liver hepatocellular carcinoma.
    Author: Yue Y, Tao J, An D, Shi L.
    Journal: Heliyon; 2024 Jan 30; 10(2):e24462. PubMed ID: 38293480.
    Abstract:
    BACKGROUND: Liver hepatocellular carcinoma (LIHC) is the third largest cause of cancer mortality. Exosomes are vital regulators in the development of cancer. However, the mechanisms regarding the association of exosome-related long non-coding RNAs (lncRNAs) in LIHC are not clear. METHODS: LIHC RNA sequences and exosome-associated genes were collected according to The Cancer Genome Atlas (TCGA), Hepatocellular Carcinoma Cell DataBase (HCCDB) and ExoBCD databases, and exosome-related lncRNAs with prognostic differential expression were screened as candidate lncRNAs using Spearman's method and univariate Cox regression analysis. Candidate lncRNAs were then used to construct a prognostic model and mRNA-lncRNA co-expression network. Differentially expressed genes (DEGs) in low- and high-risk groups were identified and enrichment analysis was performed for up- and down-regulated DEGs, respectively. The expression of immune checkpoint-related genes, immune escape potential and microsatellite instability among different risk groups were further analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) and transwell assay were applied for detecting gene expression levels and invasion and migration ability. RESULTS: Based on 17 prognostical exosome-associated lncRNAs, four hub lncRNAs (BACE1_AS, DSTNP2, PLGLA, and SNHG3) were selected for constructing a prognostic model, which was demonstrated to be an independent prognostic variable for LIHC. High risk score was indicative of poorer overall survival, lower anti-tumor immune cells, higher genomic instability, higher immune escape potential, and less benefit for immunotherapy. The qRT-PCR test verified the expression level of the lncRNAs in LIHC cells, and the inhibitory effect of BACE1_AS on immune checkpoint genes levels. BACE1_AS silence also depressed the ability of migration and invasion of LIHC cells. CONCLUSION: The Risk model constructed by exosome-associated lncRNAs could well predict immunotherapy response and prognostic outcomes for LIHC patients. We comprehensively reveal the clinical features of prognostical exosome-related lncRNAs and their potential ability to predict immunotherapeutic response of patients with LIHC and their prognosis.
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