Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Front Immunol. 2023 Sep 25;14:1187108. doi: 10.3389/fimmu.2023.1187108. eCollection 2023.
The tumor microenvironment of hepatocellular carcinoma is composed of multiple cells, and the interactive communication between cells drives tumor progression and characterizes the tumor. Communication between cells is mainly achieved through signal transduction between receptor ligands, and the rise of single-cell technology has made it possible to analyze the communication network between cells.
We applied a train of bioinformatic techniques and in vitro experiments. We analyzed the composition of the microenvironment of liver cancer by combining single-cell sequencing data and transcriptome sequencing data from liver cancer to construct molecular typing and risk models for LRs. Then, we analyzed association of it with prognosis, mutation, KEGG, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB) and drug sensitivity in liver cancer. qPCR and was used to identify SLC1A5 expression in LIHC cell lines and CCK8, transwell and cell colony formation were performed to validate the function of SLC1A5. Meanwhile, we also performed polarization of macrophages.
In this experiment, we found that liver cancer tissues are rich in immune and mesenchymal cells, and there is extensive signaling between individual cells, so we constructed molecular typing and risk models for LRs. Combining clinical data revealed significant differences in clinical characteristics, prognosis and mutated genes between the molecular typing of receptor-ligand pairs, as well as in sensitivity to drugs; similarly, there were significant prognostic differences between the risk models. There were also notable differences in activated signaling pathways, infiltrating immune cells and immune subtypes. Subsequently, we used siRNA to knock down SLC1A5 in hepatocellular carcinoma cells and found that cell proliferation, migration and invasion were diminished.
In conclusion, our LRs model may become a marker to guide clinical treatment and prognosis.
肝细胞癌的肿瘤微环境由多种细胞组成，细胞之间的相互交流促进肿瘤进展并表征肿瘤。细胞之间的通讯主要通过受体配体之间的信号转导来实现，单细胞技术的兴起使得分析细胞之间的通讯网络成为可能。
我们应用了一系列生物信息学技术和体外实验。我们通过结合肝癌的单细胞测序数据和转录组测序数据来分析肝癌微环境的组成，构建了 LR 的分子分型和风险模型。然后，我们分析了其与肝癌预后、突变、KEGG、肿瘤微环境（TME）、免疫浸润、肿瘤突变负荷（TMB）和药物敏感性的关联。qPCR 用于鉴定 LIHC 细胞系中 SLC1A5 的表达，CCK8、transwell 和细胞集落形成实验用于验证 SLC1A5 的功能。同时，我们还进行了巨噬细胞的极化。
在这项实验中，我们发现肝癌组织富含免疫细胞和间充质细胞，个体细胞之间存在广泛的信号传递，因此我们构建了 LR 的分子分型和风险模型。结合临床数据，发现受体-配体对的分子分型、药物敏感性之间的临床特征、预后和突变基因存在显著差异；同样，风险模型之间也存在显著的预后差异。激活的信号通路、浸润的免疫细胞和免疫亚型也存在显著差异。随后，我们使用 siRNA 敲低肝癌细胞中的 SLC1A5，发现细胞增殖、迁移和侵袭能力减弱。
综上所述，我们的 LR 模型可能成为指导临床治疗和预后的标志物。
