Peng Xiaozhen, Chen Ruochan, Cai Shenglan, Lu Shanshan, Zhang Yiya
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Huaihua Key Laboratory of Research and Application of Novel Molecular Diagnostic Techniques, School of Public Health & Laboratory Medicine, Hunan University of Medicine, Huaihua, China.
Front Oncol. 2021 Mar 11;11:650355. doi: 10.3389/fonc.2021.650355. eCollection 2021.
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.
SLC1A4是一种钠依赖性中性氨基酸转运体,被认为参与包括肿瘤发生在内的各种病理生物学过程。然而,SLC1A4与肝细胞癌(HCC)之间的相关性仍不清楚。在我们的研究中,进行了综合生物信息学和功能分析,以揭示SLC1A4在HCC中的预后和潜在功能。结果显示,HCC中SLC1A4的mRNA和蛋白水平升高,并且它是总生存期(OS)的一个强大的独立预后标志物。共表达基因分析和基因集富集分析(GSEA)显示,SLC1A4与细胞周期、代谢、癌症相关通路有关。此外,功能分析表明,沉默SLC1A4可抑制HCC中的细胞增殖、迁移、细胞周期,并促进细胞凋亡。接下来,免疫分析表明,SLC1A4表达与HCC中的免疫浸润和免疫相关趋化因子表达呈正相关。沉默SLC1A4明显降低了HCC细胞中这些趋化因子的表达。最后,药物敏感性分析揭示了针对SLC1A4高表达的HCC患者的五种潜在敏感性药物。总之,我们的结果表明,SLCIA4可能是HCC的一种新的预后预测指标和免疫治疗靶点,而这些敏感性药物可能是治疗SLC1A4高表达的HCC患者的有效治疗策略。