Dataset Information

Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma.

ABSTRACT: Background & aims:Hepatocellular carcinoma (HCC) has high potential for recurrence, even in curative operative cases. Although several molecular-targeting drugs have been applied to recurrent HCC, their effectiveness has been limited. This study therefore aims to develop novel cancer drugs through protein methylation. Methods:We investigated the role of KDM5B/JARID1B, a member of JmjC histone demethylase, in HCC. Expression profiles of KDM5B were examined by immunohistochemical analysis in 105 HCC clinical tissue samples. To examine functional effects of KDM5B using HCC cell lines, we performed loss-of-function analysis treated with KDM5B-specific small interfering RNAs (siKDM5B). Results:All HCC cases were divided into KDM5B-positive expression group (n=54) and negative expression group (n=51). In five-year overall survival, KDM5B-positive group had poorer prognosis than KDM5B-negative (61% vs 77%, p=0.047). KDM5B-positive group had much poorer prognosis than that of the negative group, especially in HCC derived from persistent infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) (54% vs 78%, p=0.015). Multivariate analysis indicated that KDM5B was the strongest risk factor for poor prognosis, especially in HCC derived from HBV/HCV. Inhibition of KDM5B could significantly suppress HCC cell proliferation through no promotion from G1 to S phase. Real-time PCR and Western blotting demonstrated that E2F1/E2F2 were downstream genes of KDM5B. Conclusions:Overexpression of KDM5B results in poor prognosis in HCC that especially derived from HBV/HCV. KDM5B appears to be an ideal target for the development of anti-cancer drugs.

SUBMITTER: Shigekawa Y

PROVIDER: S-EPMC6188148 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma.

Shigekawa Yoshinobu Y Hayami Shinya S Ueno Masaki M Miyamoto Atsushi A Suzaki Norihiko N Kawai Manabu M Hirono Seiko S Okada Ken-Ichi KI Hamamoto Ryuji R Yamaue Hiroki H

Oncotarget 20180928 76

<h4>Background & aims</h4>Hepatocellular carcinoma (HCC) has high potential for recurrence, even in curative operative cases. Although several molecular-targeting drugs have been applied to recurrent HCC, their effectiveness has been limited. This study therefore aims to develop novel cancer drugs through protein methylation.<h4>Methods</h4>We investigated the role of KDM5B/JARID1B, a member of JmjC histone demethylase, in HCC. Expression profiles of KDM5B were examined by immunohistochemical an ...[more]

PMID: 30344945

Similar Datasets

Project description:Purpose:Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed digestive cancers and the fourth leading cause of death worldwide. Long noncoding RNAs (lncRNAs) with key roles in HCC development and progression have emerged and are used in the diagnosis and prognostic prediction of HCC. The lncRNA gradually increased during hepatocarcinogenesis (GIHCG) is a novel lncRNA with aberrant expression in many tumors, but its prognostic value and biological role in HCC have not been fully studied. Thus, the aim of this study was to explore the expression pattern and potential biological role of GIHCG in HCC. Patients and Methods:The expression pattern of GIHCG in HCC was analyzed in our HCC cohort and validated in The Cancer Genome Atlas (TCGA) database. To assess the prognostic value of GIHCG, survival analyses and Cox regression analyses were carried out in two HCC cohorts. Functional enrichment analysis was used to predict the gene sets and pathways related to aberrant GIHCG expression. Furthermore, the relationship between GIHCG expression and immune infiltration in HCC was analyzed. Results:GIHCG was highly expressed in HCC tissues compared with normal liver tissues. In addition, high GIHCG expression was significantly correlated with inferior clinicopathological characteristics and shorter survival times. High GIHCG expression was an independent prognostic factor for overall survival and disease-free survival in the HCC cohort in our center and in the TCGA-LIHC cohort. Hallmark terms such as "G2M checkpoint", "MYC targets" and "DNA repair" were enriched in the GIHCG high-expression groups. High GIHCG expression negatively correlated with the infiltration of memory CD4+ and CD8+ T cells, natural killer cells, macrophages, dendritic cells, neutrophils and monocytes. Conclusion:The findings of our study indicate that GIHCG is a biomarker that can be used to predict the prognosis of HCC patients and is correlated with immune cell infiltration in HCC.

Dataset Information

Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma.

Publications

Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets