Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Shanghai 200065, China.
Dis Markers. 2022 May 11;2022:6304859. doi: 10.1155/2022/6304859. eCollection 2022.
Liver hepatocellular carcinoma (LIHC) has had a continuous increase in incidence and mortality rates over the last 40 years. Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) is a protein coding gene which encodes the cytoplasmic dynein heavy chain family. This is the first investigation into the expression of DYNC1H1 and its mechanisms of action in LIHC patients.
Based on the DYNC1H1 expression data from the TCGA database, we performed the DYNC1H1 expression, clinicopathological data, gene enrichment, and immune infiltration analysis. TIMER and CIBERSORT were used to assess immune responses of DYNC1H1 in LIHC. GEPIA, K-M survival analysis, and immunohistochemical staining pictures from the THPA were used to validate the results. In order to evaluate the diagnostic value of DYNC1H1, GEO datasets were analyzed by using ROC analysis. And quantitative real-time polymerase chain reaction was also carried out to evaluate the expression of DYNC1H1.
DYNC1H1 expression levels were associated with T classification, pathologic stage, histologic grade, and serum AFP levels. DYNC1H1 is an independent factor for a poor prognosis in patients with LIHC. Further study showed that high expression of DYNC1H1 was enriched in epithelial-mesenchymal transition (EMT) and the TGF signaling pathway by GSEA analysis enrichment, indicating that DYNC1H1 might play a key role in the progression of CRC through EMT and immune response, which also had been validated by the experimental assays.
DYNC1H1 will provide a novel and important perspective for the mechanisms of LIHC by regulating EMT. This gene will be able to act as an efficacious tool for the early diagnosis and effective intervention of LIHC.
在过去的 40 年中，肝肝细胞癌（LIHC）的发病率和死亡率持续上升。动力蛋白细胞质 1 重链 1（DYNC1H1）是一种蛋白质编码基因，编码细胞质动力蛋白重链家族。这是首次对 LIHC 患者中 DYNC1H1 的表达及其作用机制进行研究。
基于 TCGA 数据库中的 DYNC1H1 表达数据，我们进行了 DYNC1H1 表达、临床病理数据、基因富集和免疫浸润分析。TIMER 和 CIBERSORT 用于评估 LIHC 中 DYNC1H1 的免疫反应。GEPIA、K-M 生存分析和 THPA 的免疫组织化学染色图片用于验证结果。为了评估 DYNC1H1 的诊断价值，通过 ROC 分析分析了 GEO 数据集。还通过定量实时聚合酶链反应评估了 DYNC1H1 的表达。
DYNC1H1 的表达水平与 T 分类、病理分期、组织学分级和血清 AFP 水平有关。DYNC1H1 是 LIHC 患者预后不良的独立因素。进一步的研究表明，通过 GSEA 分析富集，高表达的 DYNC1H1 富集在上皮-间充质转化（EMT）和 TGF-β 信号通路中，这表明 DYNC1H1 可能通过 EMT 和免疫反应在 CRC 的进展中发挥关键作用，这也通过实验检测得到了验证。
DYNC1H1 通过调节 EMT 为 LIHC 的机制提供了新的重要视角。该基因将能够作为 LIHC 早期诊断和有效干预的有效工具。
