Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Department of Liver Disease, The fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
BMC Gastroenterol. 2024 Aug 14;24(1):265. doi: 10.1186/s12876-024-03346-0.
The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear.
SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses.
SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.
肿瘤微环境中免疫细胞的活性和数量与肝细胞癌（HCC）患者的总生存率密切相关。性别决定区 Y 框 4（SOX4）基因在各种肿瘤组织中异常表达，对肿瘤的发生发展至关重要。然而，SOX4 在 HCC 中的表达与肿瘤免疫的相关性尚不清楚。
利用 The Cancer Genome Atlas 和 UALCAN 数据库中的数据来探索 SOX4 的表达。使用实时逆转录定量和 Western 印迹分析几种肝癌细胞系中的 SOX4 表达。此外，使用来自 Tumor Immune Estimation Resource、Gene Expression Profiling Interactive Analysis 和 Tumor-Immune System Interactions 数据库的数据来分析 SOX4 表达与 HCC 患者的癌症免疫特征和浸润免疫细胞基因标志物集之间的相关性。此外，我们评估了 HCC 组织中的 SOX4 表达及其与生存率的相关性。随后，使用表达、相关性和生存分析来确定导致 SOX4 过表达的非编码 RNA（ncRNA）。
SOX4 在 HCC 中表达显著上调，与预后不良相关。此外，HCC 中 SOX4 的上调与免疫细胞浸润、几种免疫细胞标志物和免疫检查点表达呈正相关。最后，确定了 MCM3AP-AS1/hsa-miR-204-5p 轴是 HCC 中 SOX4 的最可能上游 ncRNA 相关途径。这些结果表明，ncRNA 介导的 SOX4 上调与 HCC 中的免疫浸润水平和不良预后相关。我们的研究结果为开发 HCC 的新型免疫治疗靶点提供了新的方向。
