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  11. Elevated Slc1a5 Associated With Poor Prognosis And Therapeutic Resistance To Transarterial Chemoembolization In Hepatocellular Carcinoma

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

Guixiong Zhang1, Yitai Xiao2, Jizhou Tan1,3

  • 1Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, Guangdong Province, 510080, P. R. China.

Journal of Translational Medicine
|June 6, 2024

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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
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View abstract on PubMed

Summary
This summary is machine-generated.

Elevated SLC1A5 expression in hepatocellular carcinoma (HCC) correlates with poor survival and resistance to transarterial chemoembolization (TACE). SLC1A5 promotes tumor growth, migration, and drug resistance, potentially via epithelial-mesenchymal transition (EMT).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent malignancy where glutamine metabolism is crucial for tumor cell survival.
  • The glutamine transporter SLC1A5's role in HCC progression and treatment response, particularly transarterial chemoembolization (TACE), requires elucidation.

Purpose of the Study:

  • To investigate the impact of SLC1A5 expression on HCC patient prognosis and TACE efficacy.
  • To explore the underlying mechanisms by which SLC1A5 influences HCC progression, including its relationship with hypoxia, angiogenesis, and immune infiltration.

Main Methods:

  • Analysis of SLC1A5 expression in HCC datasets and patient cohorts, correlating it with survival and TACE response.
  • Investigation of SLC1A5's association with hypoxia, angiogenesis, and immune cell infiltration using immunohistochemistry, immunofluorescence, and transcriptome sequencing.
Keywords:
Epithelial-mesenchymal transition (EMT)Hepatocellular carcinomaSLC1A5Transarterial Chemoembolization (TACE)

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  • Functional studies involving SLC1A5 knockdown/overexpression in HCC cell lines and xenograft models to assess proliferation, migration, apoptosis, and drug sensitivity.

    • Main Results:

    • Higher SLC1A5 expression in HCC tissues correlated with poorer survival and TACE resistance.
    • SLC1A5 expression was positively linked to hypoxia, angiogenesis, immune checkpoint pathways, and immunosuppressive cell infiltration (macrophages, Tregs).
    • SLC1A5 modulation affected HCC cell behavior, impacting proliferation, apoptosis, migration, and drug sensitivity, and was associated with epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, N-cadherin).

    Conclusions:

    • Elevated SLC1A5 is a marker for poor prognosis and TACE resistance in HCC.
    • SLC1A5 is implicated in promoting HCC progression through hypoxia, angiogenesis, and immunosuppression.
    • SLC1A5 may drive HCC cell migration and drug resistance by mediating the epithelial-mesenchymal transition (EMT) pathway.