Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning 530021, People’s Republic of China.
Aging (Albany NY). 2023 Aug 24;15(16):8408-8432. doi: 10.18632/aging.204978.
This study aimed to investigate the role of squamous cell carcinoma antigen recognized by T cells 3 (SART3) in hepatocellular carcinoma (HCC).
SART3 expression and prognostic value were analyzed in TCGA and GEO datasets. The diagnostic value and prognostic significance of SART3 were determined using immunohistochemistry in the Guangxi cohort. The whole-exome mutation spectrum of SART3 was analyzed in high and low expression groups in both TCGA and Guangxi cohorts. The biological functions of the SART3 gene were validated through experiments using small interfering RNA technology to downregulate SART3 expression in HCC cell lines.
SART3 expression was significantly higher in HCC tissues than in adjacent noncancerous liver tissues in TCGA, GEO and Guangxi cohorts. High expression of SART3 was significantly associated with poor prognosis in HCC patients. In TCGA and Guangxi cohorts, the expression of SART3 in the TP53 mutation group was significantly higher than that in the non-mutation group. Downregulation of SART3 expression significantly inhibited the migration and proliferation of HCC cells. SART3 may be involved mainly in immune infiltration of Th2 cells and macrophages in HCC. Additionally, SART3 can upregulate the expression of immune checkpoints (PD-L1 and TIM-3) and predict potential therapeutic agents for HCC.
The findings of this study demonstrate the diagnostic and prognostic value of SART3 in HCC. SART3 may be associated with immune infiltration of Th2 cells and macrophages in HCC, highlighting its potential role in the development and progression of HCC.
本研究旨在探讨 SART3 在肝细胞癌（HCC）中的作用。
分析 TCGA 和 GEO 数据集的 SART3 表达和预后价值。使用免疫组织化学方法在广西队列中确定 SART3 的诊断价值和预后意义。分析 TCGA 和广西队列中 SART3 高表达和低表达组的全外显子突变谱。通过小干扰 RNA 技术下调 HCC 细胞系中 SART3 的表达，验证 SART3 基因的生物学功能。
在 TCGA、GEO 和广西队列中，SART3 在 HCC 组织中的表达明显高于邻近的非癌性肝组织。SART3 的高表达与 HCC 患者的预后不良显著相关。在 TCGA 和广西队列中，TP53 突变组 SART3 的表达明显高于非突变组。下调 SART3 的表达显著抑制 HCC 细胞的迁移和增殖。SART3 可能主要参与 HCC 中 Th2 细胞和巨噬细胞的免疫浸润。此外，SART3 可以上调免疫检查点（PD-L1 和 TIM-3）的表达，并预测 HCC 的潜在治疗药物。
本研究结果表明 SART3 在 HCC 中的诊断和预后价值。SART3 可能与 HCC 中 Th2 细胞和巨噬细胞的免疫浸润有关，提示其在 HCC 的发生和发展中可能具有重要作用。
