Kosai-Fujimoto Yukiko, Itoh Shinji, Yugawa Kyohei, Fukuhara Takasuke, Okuzaki Daisuke, Toshima Takeo, Harada Noboru, Oda Yoshinao, Yoshizumi Tomoharu, Mori Masaki
Department of Surgery and Science, School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.
Mol Clin Oncol. 2022 Jun 23;17(2):131. doi: 10.3892/mco.2022.2564. eCollection 2022 Aug.
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.
含Jumonji结构域蛋白6（JMJD6）与各类癌症预后的相关性已得到证实，但肝内胆管癌（ICC）除外。本研究旨在阐明JMJD6对ICC的影响。对51例行ICC手术患者的肝脏标本进行免疫组织化学染色，分析JMJD6表达情况。研究临床病理因素与JMJD6表达之间的关系。同时，采用Transwell迁移试验和活力试验评估JMJD6敲低细胞的细胞活性。在临床样本的免疫组织化学染色中，51个样本中有32个出现JMJD6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）。进一步分析表明，较高的JMJD6表达是OS和RFS改善的独立预后因素之一。在ICC商业培养细胞系中敲低JMJD6表达，提取RNA和蛋白质，采用RNA测序和蛋白质印迹法分析下游基因表达。RNA测序和蛋白质印迹法显示，JMJD6敲低与程序性死亡配体1（PD-L1）表达升高有关。此外，免疫组织化学染色检测显示，JMJD6低表达临床样本中的PD-L1表达更高。总之，JMJD6高表达是ICC独立的有利预后因素。JMJD6可能通过调节PD-L1表达影响ICC的预后。
