Elevated SLC1A5 associated with poor prognosis and therapeutic resistance to transarterial chemoembolization in hepatocellular carcinoma

作者：Guixiong Zhang, Yitai Xiao, Jizhou Tan, Hang Liu, Wenzhe Fan, Jiaping Li · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05298-1 · 被引用次数：21 · 研究领域：Cancer, Hypoxia, and Metabolism、Amino Acid Enzymes and Metabolism、Cancer Research and Treatments

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor, and glutamine is vital for tumor cells. The role of glutamine transporter SLC1A5 in tumor progression and transarterial chemoembolization (TACE) efficacy is under study. This research seeks to determine the impact of SLC1A5 expression on the prognosis and TACE efficacy of HCC and elucidate its mechanisms. METHODS: SLC1A5 expression in HCC, correlation with patient outcomes, and response to TACE were studied in an open access liver cancer dataset and confirmed in our cohort. Additionally, the correlation between SLC1A5 expression and hypoxia, angiogenesis and immune infiltration was analyzed and verified by immunohistochemistry, immunofluorescence and transcriptome sequencing. Liver cancer cell lines with SLC1A5 expression knockdown or overexpression were constructed, and cell proliferation, colony formation, apoptosis, migration and drug sensitivity as well as in vivo xenograft tumor were measured. A gene set enrichment analysis was conducted to determine the signaling pathway influenced by SLC1A5, and a western blot analysis was performed to detect protein expression alterations. RESULTS: SLC1A5 expression was higher in HCC tissue and associated with poor survival and TACE resistance. Hypoxia could stimulate the upregulation of glutamine transport, angiogenesis and SLC1A5 expression. The SLC1A5 expression was positively correlated with hypoxia and angiogenesis-related genes, immune checkpoint pathways, m...