Deng Xinna, Wang Yashu, Guo Hao, Wang Qian, Rao Shuting, Wu Haijiang
Departments of Oncology, Hebei General Hospital, Shijiazhuang 050057, China.
Department of Pathology, Hebei Medical University, Shijiazhuang 050011, China.
Cancers (Basel). 2023 Oct 31;15(21):5235. doi: 10.3390/cancers15215235.
SOX4 plays an important role in tumorigenesis and cancer progression. The role of SOX4 in pan-cancer and its underlying molecular mechanism in liver hepatocellular carcinoma (LIHC) are not fully understood. In this study, a comprehensive analysis and experimental validation were performed to explore the function of SOX4 across tumor types.
Raw data in regard to SOX4 expression in malignant tumors were downloaded from the TCGA and GTEx databases. The expression levels, prognostic values, genetic mutation, and DNA promoter methylation of SOX4 across tumor types were explored via systematic bioinformatics analysis. The ceRNA regulatory network, immune characteristics, and prognostic models were analyzed in LIHC. Finally, we conducted in vitro experiments including Western blotting, cell proliferative assay, trypan blue staining, and fluorescence microscopy to further explore the function of SOX4 in LIHC.
SOX4 expression was significantly upregulated in 24 tumor types. SOX4 expression level was strongly associated with unfavorable prognoses, genetic mutations, and DNA methylation levels across different tumor types. Especially in LIHC, LINC00152/hsa-miR-139-3p/SOX4 was identified as a crucial ceRNA network. Moreover, this study also provides insight into the roles of SOX4 expression in immune cell infiltration, macrophage polarization, immune subtype, molecular subtype, and immunomodulators, as well as the tumor immune microenvironment (TIME)-related prognosis, in LIHC. The study established six favorable prognostic models to predict LIHC prognosis based on the SOX4-associated genes. Finally, lenvatinib treatment can increase the expression of SOX4 in hepatocellular carcinoma cells and lead to drug resistance. Silencing SOX4 can effectively eliminate the drug resistance caused by lenvatinib treatment and inhibit the proliferation of cancer cells.
This study highlights that SOX4 may serve as a promising therapeutic target for tumor treatment.
SOX4在肿瘤发生和癌症进展中发挥重要作用。SOX4在泛癌中的作用及其在肝细胞癌（LIHC）中的潜在分子机制尚未完全明确。本研究进行了全面分析和实验验证，以探究SOX4在不同肿瘤类型中的功能。
从TCGA和GTEx数据库下载关于SOX4在恶性肿瘤中表达的原始数据。通过系统的生物信息学分析，探究SOX4在不同肿瘤类型中的表达水平、预后价值、基因突变和DNA启动子甲基化情况。在LIHC中分析ceRNA调控网络、免疫特征和预后模型。最后，我们进行了包括蛋白质印迹、细胞增殖测定、台盼蓝染色和荧光显微镜检查在内的体外实验，以进一步探究SOX4在LIHC中的功能。
SOX4在24种肿瘤类型中表达显著上调。SOX4表达水平与不同肿瘤类型的不良预后、基因突变和DNA甲基化水平密切相关。特别是在LIHC中，LINC00152/hsa-miR-139-3p/SOX4被确定为关键的ceRNA网络。此外，本研究还深入了解了SOX4表达在LIHC中的免疫细胞浸润、巨噬细胞极化、免疫亚型、分子亚型和免疫调节剂中的作用，以及与肿瘤免疫微环境（TIME）相关的预后。该研究基于与SOX4相关的基因建立了六个预测LIHC预后的良好预后模型。最后，乐伐替尼治疗可增加肝癌细胞中SOX4的表达并导致耐药。沉默SOX4可有效消除乐伐替尼治疗引起的耐药并抑制癌细胞增殖。
本研究强调SOX4可能是肿瘤治疗的一个有前景的治疗靶点。
