Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Hepatobiliary Surgery, Weifang People's Hospital, Shandong, Weifang, Shandong, China.
Front Immunol. 2023 Jul 7;14:1158360. doi: 10.3389/fimmu.2023.1158360. eCollection 2023.
Liver hepatocellular carcinoma (LIHC) is one of the malignant tumors with high incidence as well as high death, which is ranked as the sixth most common tumor and the third highest mortality worldwide. CD93, a transmembrane protein, has been widely reported to play an important role in different types of diseases, including many types of cancer by mainly functioning in extracellular matrix formation and vascular maturation. However, there are few researches focusing on the role and potential function of CD93 in LIHC.
In this study, we comprehensively analyzed the relationship between CD93 and LIHC. We not only discovered transcriptional expression of CD93 in LIHC by using the TIMER, GEPIA and UALCAN database, but also performed WB and IHC to verify the protein expression of CD93 in LIHC. Meantime, Kaplan-Meier Plotter Database Analysis were used to assess the prognosis of CD93 in LIHC. After knowing close correlation between CD93 expression and LIHC, there were STRING, GeneMania and GO and KEGG enrichment analyses to find how CD93 functions in LIHC. We further applied CIBERSORT Algorithm to explore the correlation between CD93 and immune cells and evaluate prognostic value of CD93 based on them in LIHC patients.
The transcriptional and protein expression of CD93 were both obviously increased in LIHC by above methods. There was also a significant and close correlation between the expression of CD93 and the prognosis of LIHC patients by using Kaplan-Meier Analysis, which showed that LIHC patients with elevated expression of CD93 were associated with a predicted poor prognosis. We found that the functions of CD93 in different cancers are mainly related to Insulin like growth factor binding protein 7 Gene (IGFBP7)/CD93 pathway via STRING, GeneMania and functional enrichment analyses. Further, our data obtained from CIBERSORT Algorithm suggested CD93 was also associated with the immune response. There is a close positive correlation between CD93 expression and the infiltration levels of all six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Importantly, CD93 can affect the prognosis of patients with LIHC partially due to immune infiltration.
Our results demonstrated CD93 may be a candidate predictor of clinical prognosis and immunotherapy response in LIHC.
肝细胞肝癌（LIHC）是一种发病率和死亡率都很高的恶性肿瘤，在全球范围内排名第六的常见肿瘤和第三大死亡原因。跨膜蛋白 CD93 已被广泛报道在多种疾病中发挥重要作用，包括许多类型的癌症，主要作用是在细胞外基质形成和血管成熟中发挥作用。然而，目前针对 CD93 在 LIHC 中的作用和潜在功能的研究较少。
在这项研究中，我们全面分析了 CD93 与 LIHC 的关系。我们不仅通过 TIMER、GEPIA 和 UALCAN 数据库发现了 CD93 在 LIHC 中的转录表达，还通过 WB 和 IHC 验证了 CD93 在 LIHC 中的蛋白表达。同时，我们使用 Kaplan-Meier Plotter Database Analysis 评估了 CD93 在 LIHC 中的预后。在了解 CD93 表达与 LIHC 之间的密切相关性后，我们进行了 STRING、GeneMania 和 GO 和 KEGG 富集分析，以寻找 CD93 在 LIHC 中的作用机制。我们进一步应用 CIBERSORT 算法探索了 CD93 与免疫细胞的相关性，并基于这些相关性评估了 CD93 在 LIHC 患者中的预后价值。
通过上述方法，我们发现 CD93 的转录和蛋白表达在 LIHC 中均明显升高。Kaplan-Meier 分析表明，CD93 的表达与 LIHC 患者的预后也存在显著而密切的相关性，提示 CD93 表达升高的 LIHC 患者预后不良。通过 STRING、GeneMania 和功能富集分析，我们发现 CD93 在不同癌症中的功能主要与胰岛素样生长因子结合蛋白 7 基因（IGFBP7）/CD93 通路相关。进一步，我们从 CIBERSORT 算法获得的数据表明，CD93 还与免疫反应有关。CD93 的表达与六种类型免疫细胞（B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞）的浸润水平呈密切正相关。重要的是，CD93 部分通过免疫浸润影响 LIHC 患者的预后。
我们的研究结果表明，CD93 可能是 LIHC 临床预后和免疫治疗反应的候选预测因子。
