SLC1A4: A Powerful Prognostic Marker and Promising Therapeutic Target for HCC.

Xiaozhen Peng,Shanshan Lu,Yiya Zhang,Shenglan Cai,Ruochan Chen

doi:10.3389/fonc.2021.650355

Abstract

SLC1A4, a Na-dependent neutral amino acid transporter, was considered to participate in the various pathobiological process, including tumorigenesis. However, the correlation between SLC1A4 and Hepatocellular Carcinoma (HCC) remains unclear. In our study, integrative bioinformatics and functional profiling were performed to reveal the prognosis and potential function of SLC1A4 in HCC. The results showed that the mRNA and protein levels of SLC1A4 were elevated in HCC, and it was a powerful independent prognostic marker for overall survival (OS). The co-expressed genes analysis and GSEA analysis showed that SLC1A4 was related to cell cycle, metabolism, cancer-related pathway. Furthermore, the functional analysis revealed that silenced SLC1A4 inhibited cell proliferation, migration, cell cycle, and promoted cell apoptosis in HCC. Next, immune analysis showed that SLC1A4 expression was positively associated with immune infiltration and immune-related chemokine expression in HCC. Silenced SLC1A4 evidently reduced these chemokines expression in HCC cells. Finally, drug sensitivity analysis revealed potential five sensitivity drugs for HCC patients with high-expressed SLC1A4. In conclusion, our results suggested that SLCIA4 could be a novel predictor prognosis and immunotherapeutic targets of HCC, and the sensitivity drugs may be effective therapeutic strategy for HCC patients with high-expressed SLC1A4.

Highlights

Hepatocellular Carcinoma (HCC), a common type of primary liver cancer (PLC), which accounts for approximately 70–90% of PLC patients globally [1]
Multiple bioinformatics analysis combined with functional analysis methods were applied to explore the expression, prognostic role, and biological function of SLC1A4 in HCC
TCGA, ICGA, GCPIA, and GEO databases were used to investigate the prognostic value of SLC1A4 in HCC patients

Summary

INTRODUCTION

HCC, a common type of primary liver cancer (PLC), which accounts for approximately 70–90% of PLC patients globally [1]. For patients in the early stage of HCC, curative means of treatment, including liver transplantation, ablative therapies and surgical resection were considered to improve survival in patients with HCC. SLC1A4 ( referred to as ASCT1) belongs to the SLC1 family, which encompasses five high-affinity glutamine transporters and two neutral amino acid transporters. It is a Na-dependent neutral amino acid transporter for threonine, cysteine, serine and alanine [4]. Studies revealed the important role of SLC1A4 in early neuronal development and diseases, such as schizophrenia and visual dysfunction, developmental delay, microcephaly and hypomyelination [5]. The CD8+ T cells plays an important role of antitumor immunity in HCC [8, 9]. Comprehensive bioinformatics methods and functional analysis were performed to reveal the SLC1A4 expression, prognostic role, and biological function of SLC1A4 in HCC, providing a novel prognostic biomarker and therapeutic strategy of HCC

MATERIALS AND METHODS

RESULT

DISCUSSION

Findings

ETHICS STATEMENT