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Discover Oncology
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Open Access 01-12-2024 | Hepatocellular Carcinoma | Research

SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma

Authors: Renhou Zhi, Fan Fan

Published in: Discover Oncology | Issue 1/2024

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Abstract

Purpose

Solute carrier family 1 member 3(SLC1A3), a member of the glutamate transporter family, is implicated in the progression of gastric carcinoma and the renewal of thyroid carcinoma stem cells. The purpose of this work is to use experimental validation and bioinformatics analysis to look at the possible involvement of SLC1A3 in hepatocellular carcinoma (HCC).

Materials and methods

We examined the levels of SLC1A3 within HCC and its implications on immunological and epithelial–mesenchymal transition (EMT) features using the TCGA, ImmPort, and Molecular Signatures databases. The relationship between drug sensitivity and SLC1A3 expression was investigated using the GDSC database. Real-time quantitative polymerase chain reaction (qRT-PCR), Western blotting (WB), and cellular function assays were performed to assess SLC1A3 expression and its carcinogenic effects in HCC.

Results

According to our research, SLC1A3 overexpression in HCC is associated with a poor prognosis. Elevated levels of SLC1A3 promote HCC cell motility and invasion and can affect the prognosis of HCC by modifying immune responses and epithelial–mesenchymal transition. SLC1A3 has emerged as a novel prognostic marker in HCC and is associated with resistance to certain antitumor drugs.

Conclusion

SLC1A3 functions as a cancer-promoting factor contributing to poor HCC prognosis by affecting immune cell infiltration and regulating the EMT process. Elevated SLC1A3 expression may also serve as a predictor of treatment response to specific antitumor drugs.
Literature
1.
2.
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. 2024;74(3):229–63.PubMed
3.
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. 2021;71(3):209–49.PubMed
4.
Li L, Wang H. Heterogeneity of liver cancer and personalized therapy. Cancer Lett. 2016;379(2):191–7.PubMedCrossRef
5.
6.
Sauzay C, Petit A, Bourgeois A-M, et al. Alpha-foetoprotein (AFP): a multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta. 2016;463:39–44.PubMedCrossRef
7.
8.
Kanai Y, Clémençon B, Simonin A, et al. The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol Aspects Med. 2013;34(2–3):108–20.PubMedCrossRef
9.
Chivukula AS, Suslova M, Kortzak D, Kovermann P, Fahlke C. Functional consequences of SLC1A3 mutations associated with episodic ataxia 6. Hum Mutat. 2020;41(11):1892–905.PubMedCrossRef
10.
Jen JC, Wan J, Palos TP, Howard BD, Baloh RW. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology. 2005;65(4):529–34.PubMedCrossRef
11.
Xu L, Chen J, Jia L, Chen X, Awaleh Moumin F, Cai J. RETRACTED: SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. J Cell Mol Med. 2020;24(24):14392–404.PubMedPubMedCentralCrossRef
12.
Wang C, Wang Z, Liu W, Ai Z. CD133 promotes the self-renewal capacity of thyroid cancer stem cells through activation of glutamate aspartate transporter SLC1A3 expression. Biochem Biophys Res Commun. 2019;511(1):87–91.PubMedCrossRef
13.
Takashima Y, Hamano M, Yoshii K, et al. Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma. Int J Clin Oncol. 2023;28(3):468–81.PubMedCrossRef
14.
Cao D, Liu H, Bai L, Tang H. EMT-related gene signature: a new method for personalized risk assessment in patients with hepatocellular carcinoma. Dig Dis (Basel, Switzerland). 2023;41(2):282–95.CrossRef
15.
Wang Z, Jensen MA, Zenklusen JC. A practical guide to the Cancer Genome Atlas (TCGA). Methods Mol Biol (Clifton, NJ). 2016;1418:111–41.CrossRef
16.
17.
Edwards NJ, Oberti M, Thangudu RR, et al. The CPTAC Data Portal: a resource for Cancer Proteomics Research. J Proteome Res. 2015;14(6):2707–13.PubMedCrossRef
18.
Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia (New York, NY). 2017;19(8):649–58.CrossRef
19.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-102.PubMedPubMedCentralCrossRef
20.
Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling Tumor infiltrating Immune cells with CIBERSORT. Methods Mol Biol (Clifton, NJ). 2018;1711:243–59.CrossRef
21.
Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021;49(D1):D605-12.PubMedCrossRef
22.
Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362-8.PubMedCrossRef
23.
Yang W, Soares J, Greninger P, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41(Database issue):D955-961.PubMed
24.
Fu T, Dai L-J, Wu S-Y, et al. Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response. J Hematol Oncol. 2021;14(1):98.PubMedPubMedCentralCrossRef
25.
Giannelli G, Koudelkova P, Dituri F, Mikulits W. Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 2016;65(4):798–808.PubMedCrossRef
26.
Sonbol MB, Riaz IB, Naqvi SAA, et al. Systemic therapy and sequencing options in advanced hepatocellular carcinoma: a systematic review and network meta-analysis. JAMA Oncol. 2020;6(12):e204930.PubMedPubMedCentralCrossRef
27.
Vogel A, Saborowski A. Current strategies for the treatment of intermediate and advanced hepatocellular carcinoma. Cancer Treat Rev. 2020;82:101946.PubMedCrossRef
28.
29.
Lu C, Rong D, Zhang B, et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities. Mol Cancer. 2019;18(1):130.PubMedPubMedCentralCrossRef
30.
Wei Y, Lao X-M, Xiao X, et al. Plasma cell polarization to the immunoglobulin G phenotype in hepatocellular carcinomas involves epigenetic alterations and promotes hepatoma progression in mice. Gastroenterology. 2019;156(6):1890-e19041816.PubMedCrossRef
31.
Sung PS, Jang JW. Natural killer cell dysfunction in hepatocellular carcinoma: pathogenesis and clinical implications. Int J Mol Sci. 2018;19(11):3648.PubMedPubMedCentralCrossRef
32.
Li J, Zhang W, Xu H, et al. Barley grass juice attenuates hydrodynamic transfection-induced HCC initiation in mice. Nutr Cancer. 2023;75(2):750–60.PubMedCrossRef
33.
Huang H, Lan C, Wei Y, et al. Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration. Aging. 2024;16(7):6229–61.PubMedPubMedCentral
34.
Li R, Shang R, Li S, et al. LOXL3-promoted hepatocellular carcinoma progression via promotion of Snail1/USP4-mediated epithelial–mesenchymal transition. Environ Toxicol. 2022;37(10):2540–51.PubMedCrossRef
35.
Zhang X-H, Qian Y, Li Z, Zhang N-N, Xie Y-J. Let-7 g-5p inhibits epithelial–mesenchymal transition consistent with reduction of glioma stem cell phenotypes by targeting VSIG4 in glioblastoma. Oncol Rep. 2016;36(5):2967–75.PubMedCrossRef
36.
Zhang L-M, Zhang Y, Fei C, et al. Neutralization of IL-18 by IL-18 binding protein ameliorates bleomycin-induced pulmonary fibrosis via inhibition of epithelial–mesenchymal transition. Biochem Biophys Res Commun. 2019;508(2):660–6.PubMedCrossRef
37.
Li S, Sun R, Chen Y, Wei H, Tian Z. TLR2 limits development of hepatocellular carcinoma by reducing IL18-mediated immunosuppression. Cancer Res. 2015;75(6):986–95.PubMedCrossRef
38.
39.
Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–93.PubMedCrossRef
40.
Zheng Z, Liang W, Wang D, et al. Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: a meta-analysis. Int J Cancer. 2015;136(6):E751-759.PubMedCrossRef
41.
42.
Metadata
Title
SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma
Authors
Renhou Zhi
Fan Fan
Publication date
01-12-2024
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-024-01561-5

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