Impact of JMJD6 on intrahepatic cholangiocarcinoma.
Impact of JMJD6 on intrahepatic cholangiocarcinoma.
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DOI：
10.3892/mco.2022.2564
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发表时间：
2022-08
影响因子：
1.2
通讯作者：
中科院分区：
文献类型：
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Jumonji结构域6（JMJD 6）与各种类型的癌症的预后的关联已被证明，除了在肝内胆管癌（ICC）。本研究旨在阐明JMJD 6对ICC的影响。采用免疫组织化学染色法分析了51例因ICC接受手术的患者的肝脏标本中JMJD 6的表达。分析JMJD 6表达与临床病理因素的关系。在JMJD 6敲低的细胞中，用Transwell迁移试验和活力试验评估细胞活性。在51例临床标本的免疫组化染色中，32例标本中JMJD 6呈高表达。高表达还与总生存期（OS）和无复发生存期（RFS）的改善相关（分别为P=0.0033和0.048）。进一步分析显示，JMJD 6的高表达是OS和RFS改善的独立预后因素之一。在ICC的商业培养细胞系中敲低JMJD 6的表达，并提取RNA和蛋白，通过RNA测序和蛋白质印迹分析下游基因的表达。在RNA测序和蛋白质印迹中，JMJD 6敲低与较高的程序性死亡配体1（PD-L1）表达相关。此外，当使用免疫组织化学染色测量时，JMJD 6低表达临床样本中的PD-L1表达较高。结论：JMJD 6高表达是影响ICC预后的独立因素。JMJD 6可能通过调节PD-L1的表达而影响ICC的预后。
The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarcinoma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.