Liu Bin, Zhang Yang, Suo Jian
Department of Gastrocolorectal Surgery, The First Hospital of Jilin University, Changchun, China.
Front Genet. 2021 Jun 17;12:689585. doi: 10.3389/fgene.2021.689585. eCollection 2021.
Previous studies reported that pyruvate dehydrogenase kinase 4 (PDK4) is closely related to diabetes, heart disease, and carcinomas. Nevertheless, the role of PDK4 in gastric cancer (GC) occurrence and development is yet poorly understood. Our experiments were taken to evaluate PDK4's function in GC. The Cancer Genome Atlas tumor genome map database was employed to validate the levels of PDK family in different grades and stages of GC. The survival ratio of PDK families in GC was detected by the Kaplan-Meier plotter database. The links existing in the expression of PDK family and the level of tumor-infiltrating immune cells were investigated by tumor immunity assessment resource (TIMER). PDK4-associated signal pathways in GC were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway analysis. PDK4 mRNA level in the GC cells was measured by qRT-PCR. Cell counting kit-8 and Transwell assays were separately carried out to evaluate PDK4-induced influence on GC cell proliferation, migration, and invasion. Our data suggested that GC cells highly expressed PDK4, and PDK4 expression presented a significant relation with the staging, grade, and survival rate of GC. PDK4 expression presented a positive correlation with the types of different infiltrating immune cells, comprising B cells, CD4 T cells, and dendritic cells. Meanwhile, PDK4 expression exhibited a strong association with macrophages. Survival analysis revealed that the expression of PDK4 displayed a relationship with the prognosis of patients. Therefore, PDK4 was liable to be a biomarker for prognosis. Our results further displayed that PDK4 might modulate the glycolysis level in GC cells, and its expression was associated with GC cell proliferation, migration, and invasion. These data may provide insights into designing a new treatment strategy for GC.
以往研究报道，丙酮酸脱氢酶激酶4（PDK4）与糖尿病、心脏病和癌症密切相关。然而，PDK4在胃癌（GC）发生发展中的作用仍知之甚少。我们进行了实验以评估PDK4在GC中的功能。利用癌症基因组图谱肿瘤基因组图谱数据库来验证不同分级和分期的GC中PDK家族的水平。通过Kaplan-Meier绘图仪数据库检测GC中PDK家族的生存率。通过肿瘤免疫评估资源（TIMER）研究PDK家族表达与肿瘤浸润免疫细胞水平之间存在的联系。通过京都基因与基因组百科全书通路分析来分析GC中与PDK4相关的信号通路。通过qRT-PCR测量GC细胞中PDK4 mRNA水平。分别进行细胞计数试剂盒-8和Transwell实验，以评估PDK4对GC细胞增殖、迁移和侵袭的影响。我们的数据表明，GC细胞高表达PDK4，且PDK4表达与GC的分期、分级和生存率呈显著相关。PDK4表达与包括B细胞、CD4 T细胞和树突状细胞在内的不同浸润免疫细胞类型呈正相关。同时，PDK4表达与巨噬细胞密切相关。生存分析显示，PDK4的表达与患者预后有关。因此，PDK4很可能是一种预后生物标志物。我们的结果进一步表明，PDK4可能调节GC细胞中的糖酵解水平，其表达与GC细胞增殖、迁移和侵袭有关。这些数据可能为设计GC的新治疗策略提供见解。
