目的

基于生信分析溶质载体家族29 成员3（SLC29A3）基因在肝癌中的表达水平及其与预后、临床分期、免疫细胞浸润、微卫星不稳定性及肿瘤突变负荷的关系。

方法

TCGA 数据库分析泛癌中SLC29A3 表达，从TCGA 数据库获得肝癌和癌旁组织SLC29A3 mRNA 表达数据，比较SLC29A3 在肝癌组织及癌旁组织表达差异。采用Kaplan-Meier Plotter 进行生存预后分析， Cox 单变量和多变量回归分析生存预后影响因素。通过R 软件GSVA 包进行基因表达与通路得分相关性分析。

结果

TCGA 数据库分析显示，SLC29A3 在多种肿瘤高表达；基于TCGA 数据库RNA-seq 数据，获得371 例肝癌及50 例癌旁样本SLC29A3 基因信息，结果显示肝癌组织SLC29A3 相对表达量为2.7±0.6，明显高于正常癌旁组织的2.2±0.5（t=5.529，P＜0.05）。Kaplan-Meier 生存分析显示，SLC29A高表达组肝癌患者中位生存时间是37.2 个月，低表达组80.4 个月，SLC29A3 高表达组肝癌患者预后更差（HR=2.209，P＜0.05）。Cox 单因素和多因素回归分析显示，SLC29A3 高表达是肝癌患者预后差的独立危险因素（HR=1.67，95%CI：1.25～2.23；P＜0.05）。相关性分析显示，肝癌SLC29A3 高表达与肿瘤增殖相关信号、肿瘤炎性反应及PI3K-AKT-mTOR 通路正相关（r_s=0.32，0.12，0.27；P＜0.05）；SLC29A3高表达与调节性T 细胞（Treg）、髓源性抑制细胞（MDSC）、癌相关成纤维细胞（CAFs）浸润成正相关（r_s=0.31，0.28，0.16；P＜0.05），SLC29A3 高表达与微卫星不稳定性（MSI）得分亦正相关（r_s=0.11，P＜0.05）。

结论

SLC29A3 在肝癌中表达升高，其高表达与肝癌患者不良预后相关。SLC29A3 高表达可通过引发Treg、MDSC、CAFs 的浸润以及微卫星不稳定性，诱导肿瘤增殖、炎症和激活PI3K-AKTmTOR 信号通路，从而调控肝癌的进展。

Objective

To analyze the expression level of solute carrier family 29 member 3（SLC29A3） gene in liver cancer and its relationship with prognosis， clinical stage， immune cell infiltration，microsatellite instability and tumor mutational load.

Methods

Pan-cancer analysis of SLC29A3 expression was analyzed with TCGA database.The expression data of SLC29A3 mRNA in liver cancer and adjacent tissues were obtained from TCGA database， and SLC29A3 expression levels were compared between liver cancer and adjacent tissues.Survival analysis was performed by Kaplan-Meier Plotter.Prognostic factors were identified by univariate and multivariate Cox regression analyses.The correlation between gene expression and pathway score was analyzed by GSVA package of R software.

Results

TCGA database analysis showed that SLC29A3 was highly expressed in multiple tumors.The genetic information of SLC29A3 was obtained from 371 cases of liver cancer tissue samples and 50 cases of adjacent tissue samples based on RNA-seq data from TCGA database.The results revealed that the relative expression of SLC29A3 in liver cancer tissues was 2.7±0.6， significantly higher than 2.2±0.5 in normal liver tissues （t=5.529， P＜0.05）.Kaplan-Meier survival analysis showed that the median survival time of liver cancer patients with high expression of SLC29A was 37.2 months， 80.4 months for those with low expression of SLC29A.The prognosis of liver cancer patients with high expression of SLC29A was even worse （HR=2.209， P＜0.05）.Univariate and multivariate Cox regression analyses demonstrated that high expression of SLC29A3 was an independent risk factor for poor prognosis in patients with liver cancer （HR=1.67， 95%CI： 1.25-2.23； P＜0.05）.Correlation analysis showed that high expression of SLC29A3 in liver cancer was positively correlated with tumor proliferation-related signals， tumor inflammatory response and PI3K-AKT-mTOR signaling pathway （r_s=0.32， 0.12， 0.27； all P＜0.05）.High expression of SLC29A3 was positively correlated with the infiltration of regulatory T cells（Treg）， myeloid suppressor cells （MDSC） and cancer-associated fibroblasts （CAFs） （r_s=0.31， 0.28， 0.16； all P＜0.05）， and high expression of SLC29A3 was also positively correlated with microsatellite instability （MSI）score （r_s=0.11， P＜0.05）.

Conclusions

SLC29A3 expression is up-regulated in liver cancer， and its high expression is associated with poor prognosis.High expression of SLC29A3 can induce tumor proliferation，inflammation and activation of PI3K-AKT-mTOR signaling pathway by provoking the infiltration of Treg，MDSC and CAFs and MSI， thereby regulating the progression of liver cancer.