Molecular Medicine and Cancer Research Center, Basic Medicine College, Chongqing Medical University, Chongqing, People's Republic of China.
Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, People's Republic of China.
Mol Carcinog. 2023 Jun;62(6):786-802. doi: 10.1002/mc.23524. Epub 2023 Mar 17.
Dynamin 1 Like (DNM1L), a member of dynamin superfamily capable of mediating mitochondrial outer membrane division, plays a key role in the progression of different types of tumors. However, the prognostic value, clinical significance of DNM1L and its specific mechanism involved in tumorigenesis of hepatocellular carcinoma (HCC) have not been investigated clearly. In this study, we found that the expression of DNM1L were significantly higher in HCC tissues than adjacent/normal liver tissues based on multiple data sets obtained from TCGA, GEO and ONCOMINE database, also its protein expression form Drp1 is significantly higher in HCC tissues than adjacent tissues, and is related to the degree of differentiation. Kaplan-Meier curves suggested that high DNM1L expression prominently correlated with poorer overall survival, progression-free survival, relapse-free survival and disease-specific survival. Multivariate analysis showed that higher DNM1L expression was independent prognostic factors of shorter overall survival and disease-free survival. Kyoto Encyclopedia of Genes and Genomes and Gene set enrichment analysis analysis combined with validation experiments revealed the regulatory role of DNM1L on key molecules in the metabolism of xenobiotics by cytochrome p450 pathway, and DNM1L may also affects invasion and metastasis capability of HCC by mediating extracellular matrix -receptor interaction pathway. Moreover, analysis showed that higher DNM1L, CYP2C9, CYP3A4, CYP1A2 expression were associated with the resistance to sorafenib therapy. TIMER and CIBERSORT analysis indicated that the increase of DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment. Taken together, the above results indicated that DNM1L could be able to serve as a promising independent predictor and therapeutic target for HCC patients.
动力蛋白 1 样蛋白（DNM1L）是能够介导线粒体外膜分裂的动力蛋白超家族的成员，在多种类型肿瘤的进展中发挥关键作用。然而，DNM1L 的预后价值、临床意义及其在肝细胞癌（HCC）发生中的具体机制尚不清楚。在本研究中，我们基于 TCGA、GEO 和 ONCOMINE 数据库获得的多个数据集发现，DNM1L 在 HCC 组织中的表达明显高于相邻/正常肝组织，其蛋白表达形式 Drp1 在 HCC 组织中的表达也明显高于相邻组织，且与分化程度有关。Kaplan-Meier 曲线表明，高 DNM1L 表达与总生存期、无进展生存期、无复发生存期和疾病特异性生存期较差显著相关。多变量分析表明，较高的 DNM1L 表达是总生存期和无病生存期较短的独立预后因素。京都基因与基因组百科全书和基因集富集分析结合验证实验表明，DNM1L 对细胞色素 P450 途径中异生物质代谢的关键分子具有调节作用，DNM1L 还可能通过介导细胞外基质-受体相互作用途径影响 HCC 的侵袭和转移能力。此外，分析表明，较高的 DNM1L、CYP2C9、CYP3A4、CYP1A2 表达与索拉非尼治疗耐药相关。TIMER 和 CIBERSORT 分析表明，DNM1L 表达的增加可能会影响肿瘤微环境中免疫细胞的浸润。综上所述，上述结果表明，DNM1L 可能成为 HCC 患者有前途的独立预测因子和治疗靶点。
