Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
Hospital of Integrated Chinese and Western Medicine , Tianjin 300100, China.
Dig Liver Dis. 2024 Aug;56(8):1382-1399. doi: 10.1016/j.dld.2024.01.182. Epub 2024 Jan 29.
NDRG1, the first member of the NDRG family, is a multifunctional protein associated with carcinogenesis. Its function in human cancer is currently poorly understood. The aim of this study was to explore the importance of NDRG1 in tumor immune cell infiltration and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma.
NDRG1 expression in various cancers was analyzed using TIMER 2.0, the Human Protein Atlas (HPA), UALCAN and PrognoScan. Wound healing, Transwell, MTT and colony formation assays were performed to confirm the effects of NDRG1 on the metastasis and proliferation of HCC cells. Western blotting was used to study the effect of NDRG1 on the expression of EMT-related proteins. Signaling networks were constructed using LinkedOmics and Metascape. TIMER2.0 and TISIDB were used for comprehensive analysis of tumor-infiltrating immune cells and tumor-infiltrating lymphocytes (TILs).
NDRG1 expression was higher in HCC tissue than in normal liver tissue at both the mRNA and protein levels. Overexpression of NDRG1 is associated with poor prognosis in HCC patients. Genomic analysis suggests that NDRG1 promoter hypermethylation leads to enhanced transcription, which may be one mechanism for NDRG1 upregulation in HCC. The overexpression of NDRG1 promotes the invasion, migration, and proliferation of HCC cells and induces the expression of EMT-related proteins. Immunoinfiltration analysis suggests that NDRG1 is involved in the recruitment of immune cells.
The present study showed that NDRG1 may induce metastasis and invasion through EMT and immune cell infiltration. NDRG1 could be used as a biomarker for the diagnosis and prognosis of HCC and could be a potential therapeutic target in HCC.
NDRG1 是 NDRG 家族的第一个成员，是一种与致癌作用相关的多功能蛋白。其在人类癌症中的功能目前知之甚少。本研究旨在探讨 NDRG1 在肝癌肿瘤免疫细胞浸润和上皮-间充质转化（EMT）中的重要性。
使用 TIMER 2.0、人类蛋白质图谱（HPA）、UALCAN 和 PrognoScan 分析 NDRG1 在各种癌症中的表达。通过划痕愈合、Transwell、MTT 和集落形成实验证实 NDRG1 对 HCC 细胞转移和增殖的影响。Western blot 用于研究 NDRG1 对 EMT 相关蛋白表达的影响。使用 LinkedOmics 和 Metascape 构建信号网络。使用 TIMER2.0 和 TISIDB 对肿瘤浸润免疫细胞和肿瘤浸润淋巴细胞（TIL）进行综合分析。
NDRG1 在 HCC 组织中的 mRNA 和蛋白水平均高于正常肝组织。NDRG1 的高表达与 HCC 患者的不良预后相关。基因组分析表明，NDRG1 启动子的过度甲基化导致转录增强，这可能是 HCC 中 NDRG1 上调的一种机制。NDRG1 的过表达促进 HCC 细胞的侵袭、迁移和增殖，并诱导 EMT 相关蛋白的表达。免疫浸润分析表明，NDRG1 参与免疫细胞的募集。
本研究表明，NDRG1 可能通过 EMT 和免疫细胞浸润诱导转移和侵袭。NDRG1 可作为 HCC 诊断和预后的生物标志物，并可能成为 HCC 的潜在治疗靶点。
