Zhao Zhuo, Li Lingxia, Liu Yan, Shi Lei, Yuan Meijie, Shi Hongshuo, Ji Qing, Liu Guobin, Sun Jian
Department of Peripheral Vascular Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Clinical Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Oncol. 2024 Oct 24;14:1453795. doi: 10.3389/fonc.2024.1453795. eCollection 2024.
Mitochondrial fusion and fission are critical for the morphology and function of cells. DNM1L encodes dynamin-related protein 1 (DRP1), a key protein mediating mitochondrial fission, which is upregulated in a variety of cancers and is strongly associated with tumorigenesis. We aim to investigate the relationship between DNM1L and the prognosis of gastric cancer, as well as to explore the function and mechanism of DNM1L in gastric cancer (GC).
In this study, we analyzed the expression differences of DNM1L in gastric cancer tissues and paracancerous tissues using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. This was followed by validation through tissue microarrays. We then utilized the cohort information from these microarrays to explore the relationship between DNM1L expression and gastric cancer prognosis. Furthermore, we conducted enrichment analysis to investigate the function and mechanisms of DNM1L in gastric cancer, and lastly, we performed immune cell infiltration analysis using the CIBERSORT algorithm.
We discovered that the expression of DNM1L is elevated in GC tissues. TCGA data showed that the overexpression of DNM1L was positively correlated with the T-stage of GC but not with lymph node metastasis, which was also corroborated by our immunohistochemistry experiments. Based on the Kaplan-Meier curves, the high DNM1L expression was remarkably correlated with poor overall survival in patients with GC. In addition, results of COX regression analysis indicated that high DNM1L expression was an independent prognostic factor in patients with GC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) showed that DNM1L was closely associated with multiple signaling pathways and immune responses. CIBERSORT analysis indicated that increased DNM1L expression may affect the infiltration of immune cells in the tumor microenvironment.
The results of this study indicate that DNM1L is upregulated in gastric cancer (GC) and positively correlates with the T-stage and poor prognosis of GC patients, and it plays an important role in tumor immune infiltration.
线粒体融合与分裂对细胞的形态和功能至关重要。DNM1L编码动力相关蛋白1（DRP1），这是一种介导线粒体分裂的关键蛋白，在多种癌症中上调，且与肿瘤发生密切相关。我们旨在研究DNM1L与胃癌预后之间的关系，并探索DNM1L在胃癌（GC）中的功能及机制。
在本研究中，我们使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）分析了DNM1L在胃癌组织和癌旁组织中的表达差异。随后通过组织芯片进行验证。接着，我们利用这些芯片的队列信息来探究DNM1L表达与胃癌预后之间的关系。此外，我们进行了富集分析以研究DNM1L在胃癌中的功能和机制，最后，我们使用CIBERSORT算法进行免疫细胞浸润分析。
我们发现DNM1L在GC组织中表达升高。TCGA数据显示，DNM1L的过表达与GC的T分期呈正相关，但与淋巴结转移无关，我们的免疫组化实验也证实了这一点。基于Kaplan-Meier曲线，高DNM1L表达与GC患者的总生存期较差显著相关。此外，COX回归分析结果表明，高DNM1L表达是GC患者的独立预后因素。基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）表明，DNM1L与多种信号通路和免疫反应密切相关。CIBERSORT分析表明，DNM1L表达增加可能会影响肿瘤微环境中免疫细胞的浸润。
本研究结果表明，DNM1L在胃癌（GC）中上调，与GC患者的T分期和不良预后呈正相关，并且在肿瘤免疫浸润中起重要作用。
