Zou Jinhua, Wang Hui, Zhang Dongyan
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Feb 20;45(2):269-284. doi: 10.12122/j.issn.1673-4254.2025.02.08.
To investigate the clinical significance of SLC1A5 overexpression in pan-cancer and its mechanism for promoting hepatocellular carcinoma (HCC) progression.
We analyzed the correlation of SLC1A5 expression with clinical stage, lymph node metastasis and prognosis in pan-cancer using TCGA and ICGC datasets and explored its association with immune cell infiltration using EPIC, CIBERSORT, and TIMER algorithms. In HCC cell lines, the effects of lentivirus-mediated SLC1A5 overexpression or RNA interference on cell proliferation were examined using CCK-8 assay, and the growth of HCC cell xenografts overexpressing SLC1A5 was observed in nude mice. The effects of SLC1A5 overexpression or silencing in HCC cells on macrophage polarization were evaluated in a cell co-culture system.
SLC1A5 was mainly localized on cell membrane and was highly expressed in most cancers in association with clinical stage, lymph node metastasis and poor prognosis. SLC1A5 expression was positively correlated with immunity score in 13 cancer types, especially in low-grade glioma (LGG), LIHC and thyroid cancer. SLC1A5 was positively correlated with macrophage infiltration level in LGG and LIHC but negatively correlated with macrophage infiltration in 5 cancers including lung squamous carcinoma, pancreatic carcinoma, and gastric carcinoma. Patients with SLC1A5 overexpression and high level of M2 macrophage infiltration had the worst survival outcomes. SLC1A5 was correlated with immunosuppression-related genes, cytokines, and cytokine receptors, which was the most obvious in LGG and LIHC. SLC1A5 was highly expressed in different HCC cell lines, and its overexpression promoted HCC cell proliferation both and in nude mice. In the cell co-culture experiment, SLC1A5 was positively correlated with the molecular markers of M2 polarization of macrophages, and its overexpression strongly promoted M2 polarization of the macrophages and inhibited T cell secretion of IFN-γ.
SLC1A5 expression level is correlated with clinical stage, lymph node metastasis, prognosis, and immune cell infiltration in most cancers, and its overexpression promotes HCC progression by inhibiting T-cell function promoting M2 polarization of macrophages.
探讨溶质载体家族1成员5（SLC1A5）在泛癌中的过表达的临床意义及其促进肝细胞癌（HCC）进展的机制。
我们使用癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）数据集分析了SLC1A5表达与泛癌临床分期、淋巴结转移及预后的相关性，并使用免疫细胞比例推断（EPIC）、CIBERSORT和肿瘤免疫估计资源（TIMER）算法探索其与免疫细胞浸润的关联。在肝癌细胞系中，使用细胞计数试剂盒-8（CCK-8）检测慢病毒介导的SLC1A5过表达或RNA干扰对细胞增殖的影响，并在裸鼠中观察过表达SLC1A5的肝癌细胞异种移植瘤的生长情况。在细胞共培养系统中评估肝癌细胞中SLC1A5过表达或沉默对巨噬细胞极化的影响。
SLC1A5主要定位于细胞膜，在大多数癌症中高表达，与临床分期、淋巴结转移及预后不良相关。SLC1A5表达在13种癌症类型中与免疫评分呈正相关，尤其是在低级别胶质瘤（LGG）、肝癌（LIHC）和甲状腺癌中。SLC1A5在LGG和LIHC中与巨噬细胞浸润水平呈正相关，但在包括肺鳞癌、胰腺癌和胃癌在内的5种癌症中与巨噬细胞浸润呈负相关。SLC1A5过表达且M2巨噬细胞浸润水平高的患者生存结局最差。SLC1A5与免疫抑制相关基因、细胞因子和细胞因子受体相关，在LGG和LIHC中最为明显。SLC1A5在不同肝癌细胞系中高表达，其过表达在体外和裸鼠体内均促进肝癌细胞增殖。在细胞共培养实验中，SLC1A5与巨噬细胞M2极化的分子标志物呈正相关，其过表达强烈促进巨噬细胞的M2极化并抑制T细胞分泌γ干扰素（IFN-γ）。
SLC1A5表达水平与大多数癌症的临床分期、淋巴结转移、预后及免疫细胞浸润相关，其过表达通过抑制T细胞功能和促进巨噬细胞M2极化促进肝癌进展。
