Department of Iinterventional Therapy, the People's Hospital of Jianhu, Jianhu, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2017 Oct;21(17):3821-3826.
In this study, we studied the expression profile of SOX12 gene in different pathological stages of hepatocellular carcinoma (HCC) and explored the possible downstream genes related to its regulation of HCC invasion and migration.
Bioinformatic data mining was performed in liver cancer cohort in TCGA. HepG2 cells were used as in vitro cell model to assess the effect of SOX12 on CDK4 and IGF2BP1 expression. The association between the expression of SOX12, CDK4 or IGF2BP1 and survival time in HCC patients was also assessed based on the data in TCGA.
The regional lymph node metastasis (N1) and distant metastasis (M1) cases had significantly increased SOX12 expression than the lymph node negative (N0) and distant metastasis negative (M0) cases respectively. CDK4 and IGF2BP1 were among the top 20 SOX12 co-upregulated genes in HCC, which have well characterized enhancing the effect on HCC cell growth, invasion, and metastasis. In HepG2 cells, knockdown of SOX12 reduced IGF2BP1 and CDK4 expression, while enforced SOX12 expression significantly enhanced their expression. Low SOX12 or CDK4 expression was associated with significantly better 3-year survival and better 5-year survival. Low IGF2BP1 expression was associated with significantly better 3-year survival in HCC patients.
SOX12 upregulation is associated with regional and distant metastasis of HCC. SOX12 can increase the expression of CDK4 and IGF2BP1, which confer malignant phenotypes to HCC. The expression of SOX12, IGF2BP1 or CDK4 might be potential clinical prognostic markers for HCC.
本研究旨在探讨 SOX12 基因在肝细胞癌（HCC）不同病理阶段的表达谱，并探讨其调节 HCC 侵袭和迁移的可能下游相关基因。
在 TCGA 肝癌队列中进行生物信息学数据挖掘。HepG2 细胞用作体外细胞模型，以评估 SOX12 对 CDK4 和 IGF2BP1 表达的影响。还根据 TCGA 中的数据评估了 SOX12、CDK4 或 IGF2BP1 的表达与 HCC 患者生存时间之间的关联。
区域淋巴结转移（N1）和远处转移（M1）病例的 SOX12 表达明显高于无淋巴结转移（N0）和无远处转移（M0）病例。CDK4 和 IGF2BP1 是 HCC 中前 20 个 SOX12 共上调基因之一，它们具有增强 HCC 细胞生长、侵袭和转移的特征。在 HepG2 细胞中，SOX12 敲低降低了 IGF2BP1 和 CDK4 的表达，而强制表达 SOX12 则显著增强了它们的表达。低 SOX12 或 CDK4 表达与 3 年生存率显著提高和 5 年生存率显著提高相关。IGF2BP1 低表达与 HCC 患者 3 年生存率显著提高相关。
SOX12 的上调与 HCC 的局部和远处转移有关。SOX12 可以增加 CDK4 和 IGF2BP1 的表达，从而赋予 HCC 恶性表型。SOX12、IGF2BP1 或 CDK4 的表达可能是 HCC 的潜在临床预后标志物。
