Abstract
Solute Carrier Family 38 Member 1 (SLC38A1) is a principal transporter of glutamine and plays a crucial role in the transformation of neoplastic cells. However, the correlation between SLC38A1 expression, prognosis, and immune infiltration in hepatocellular carcinoma (HCC) has yet to be elucidated. We used two independent patient cohorts, namely, a Cancer Genome Atlas (TCGA) cohort and a Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, to analyze the role of SLC38A1 in HCC at the mRNA and protein levels, respectively. In these two cohorts, SLC38A1 mRNA and protein expression levels were higher in HCC tissues than in adjacent nontumor tissues. Both SLC38A1 mRNA and protein expression were positively associated with clinicopathological characteristics (clinical stage, T stage, pathological grade, tumor size, and tumor thrombus), were negatively associated with survival, and were independent prognostic factors in HCC patients. Functional enrichment analyses further indicated that SLC38A1 was involved in multiple pathways related to amino acid metabolism, tumors, and immunity. High expression levels of SLC38A1 were inversely proportional to CD8+ T cells and directly proportional to macrophages M0, neutrophils, programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Moreover, we used immunohistochemical analysis of tissue samples and other online databases to further validate the expression levels and prognostic significance of SLC38A1 in HCC. Collectively, our study demonstrated that the upregulated expression of SLC38A1 was related to an unfavorable prognosis and defective immune infiltration in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the fourth leading cause of global cancer-related deaths [1]
We found that high expression levels of SLC38A1 were significantly associated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) (p 0.002, p 0.003, p 0.009, respectively; Figures 3(a) and 3(c)). en, we used the online Kaplan–Meier plotter database to validate the prognostic value of SLC38A1 in HCC and obtained results that were consistent with the the following websites: e Cancer Genome Atlas (TCGA) database (Figures 3(d) and 3(e))
We identified a total of 85 signaling pathways that were differentially enriched in the high expression SLC38A1 phenotype (Supplementary Table 2). e most typically enriched signaling pathways are shown in Figure 7; analysis showed that multiple pathways that are related to tumor and immunity were differentially enriched in the high expression SLC38A1 phenotype
Summary
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the fourth leading cause of global cancer-related deaths [1]. Glutamine has a large number of vital functions in mammalian cells; the dysregulation of the SLC38 transporter may result in tumorigenesis and the progression of cancers [6]. The main function of SLC38A1 is to regulate the transport of short chain neutral amino acids, including glutamine. The correlation between SLC38A1 expression and immune infiltration in HCC has yet to be determined. We further validated the differential expression levels of SLC38A1 between HCC and adjacent nontumor tissue by performing immunohistochemistry (IHC) on our tissue samples. Ese analyses demonstrated that SLC38A1 was expressed at higher levels in HCC and associated with an unfavorable prognosis and defective immune infiltration
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