GSE171974
JMJD6 is a possible epigenetic regulator of PD-L1 expression and an independent favorable prognostic factor of intrahepatic cholangiocarcinoma
Association of Jumonji domain-containing 6 (JMJD6) with outcomes of various cancers has been shown, however the impact on intrahepatic cholangiocarcinoma (ICC) has never been reported yet. The aim of this study is to clarify the role of JMJD6 in the clinical settings and the impact on the outcomes of ICC. The resected liver specimens of 53 patients who underwent surgery for ICC were analyzed for JMJD6 expression by immunohistochemistry staining. The relationship between clinicopathological factors and the JMJD6 expression was investigated. Commercial culture cell lines derived from primary ICC were incubated with siRNA to decrease the expression of JMJD6. The RNA and protein were extracted to analyze the downstream gene expression with RNA-sequence and western blotting. The relationship between JMJD6 expression and tumor immunological factors were evaluated. Low expression of JMJD6 was significantly associated with poor overall survival (OS, p=0.0024). The further analyses revealed that the higher expression of JMJD6 was one of the independent better prognostic factors. ICC cells with JMJD6 knockdown revealed significantly higher programmed death-ligand 1 (PD-L1) expression (p=0.0410) in RNA-seq. The western blotting showed the result matching with the RNA-seq. H3K4me3 histone protein expression was also upregulated under the knockdown of JMJD6. A higher CD8+ T cell count combined with high expression of JMJD6 was one of the significant indicators of better prognosis both in PFS and OS. In vitro experiments proved that JMJD6 regulated the expression of PD-L1 and the paired evaluation of JMJD6 and the immune status was one of the useful factors to stratify the prognosis of ICC. Our results suggest that JMJD6 could influence the prognosis of ICC through the epigenetic regulation of PD-L1 expression. Overall design: To explore more of the importance of JMJD6 in ICC, SSP-25 cells knocked down for JMJD6 were analyzed by RNA-sequencing.