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TESC 与不良预后相关,增强肝癌的癌症干性和迁移能力。

TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer.

机构信息

Infection Medicine Research Institute of Panyu District, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Affiliated Cancer Hospital and Institute, Guangzhou Medical University, Guangzhou, Guangdong, China.

出版信息

Clin Exp Med. 2024 Aug 29;24(1):206. doi: 10.1007/s10238-024-01469-y.

Abstract

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan-Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial-mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer.

摘要

肝癌干细胞(LCSCs)是导致肝癌复发、转移和耐药的罪魁祸首。然而,诱发 LCSCs 的基因尚未被完全确定。基于我们之前的研究,我们发现钙结合 EF 手蛋白 tescalcin(TESC)在染色质重塑、转录调控和表观遗传修饰中发挥着关键作用,在球体培养的 LCSCs 中表达上调。通过搜索癌症基因组图谱、国际癌症基因组联盟、人类蛋白质图谱和 Kaplan-Meier Plotter 数据库,我们发现 TESC 在肝癌中的表达明显高于正常肝组织,并且与总生存率降低相关。多变量 Cox 分析显示 TESC 是生存的独立预后因素。高 TESC 表达与癌症干细胞途径、癌症干细胞表面标志物、干性转录因子、上皮-间充质转化(EMT)因子、免疫检查点蛋白以及肝癌中的各种癌症相关生物学过程呈正相关。此外,TESC 通过影响 EMT 来促进癌症干细胞特性。我们证明 TESC 是一种新的与干性相关的基因,可以作为肝癌的独立预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec3/11362204/4f704dc5a539/10238_2024_1469_Fig1_HTML.jpg

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