Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma

Xue-Yan Kui; Yan Gao; Xu-Sheng Liu; Jing Zeng; Jian-Wei Yang; Lu-Meng Zhou; Xiao-Yu Liu; Yu Zhang; Yao-Hua Zhang; Zhi-Jun Pei

doi:10.3389/fonc.2022.809847

Comprehensive Analysis of SLC17A9 and Its Prognostic Value in Hepatocellular Carcinoma

Front Oncol. 2022 Jul 25:12:809847. doi: 10.3389/fonc.2022.809847. eCollection 2022.

Authors

Xue-Yan Kui¹, Yan Gao², Xu-Sheng Liu², Jing Zeng³, Jian-Wei Yang⁴, Lu-Meng Zhou⁵, Xiao-Yu Liu², Yu Zhang², Yao-Hua Zhang², Zhi-Jun Pei^{1

2

6}

Affiliations

¹ Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
² Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
³ Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁴ Department of Nuclear Medicine, Xiangyang Cenral Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
⁵ Department of Nuclear Medicine, Huanggang Central Hospital, Huanggang, China.
⁶ Hubei Key Laboratory of Embryonic Stem Cell Research, Shiyan, China.

Abstract

Background: Solute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear.

Methods: The expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene-gene interaction (GGI), and protein-protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis.

Results: SLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770-0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4⁺ T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001).

Conclusion: Our data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.

Keywords: SLC17A9; TCGA; ferroptosis; hepatocellular carcinoma; immune infiltration; m6A modification.