Association of JMJD2B and Hypoxia-Inducible Factor 1 Expressions with Poor Prognosis in Osteosarcoma

Abstract

Background. JMJD2B has been reported to be implicated in malignant tumors. This study is aimed at exploring the expression and prognostic significance of JMJD2B in osteosarcoma and its association with hypoxia-inducible factor 1 (HIF1). Methods. The histopathological and clinical characteristics were retrospectively reviewed from 53 osteosarcoma patients. JMJD2B and HIF1 were examined by immunohistochemical staining of paraffin-embedded osteosarcoma samples, and their association with clinical characteristics was examined by Spearman’s test. Overall survival was examined by Kaplan-Meier analysis, and prognostic factors were identified by univariate and multivariate regression analyses. Results. JMJD2B and HIF1 expression levels were both significantly associated with Enneking stage, distant metastasis, and neoadjuvant chemotherapy, and the JMJD2B and HIF1 expressions were positively correlated (p<0.001, R=0.752). In addition, univariate analysis showed that the expression of both JMJD2B and HIF1 was significantly associated with overall survival, but multivariate analysis showed that only JMJD2B expression was significantly associated with overall survival in osteosarcoma patients. Conclusions. JMJD2B and HIF1 expression levels show significant correlation with osteosarcoma progression, and JMJD2B could predict poor prognosis of osteosarcoma patients.

Comprehensive Analysis of 5-Methylcytosine Profiles of Messenger RNA in Human High-Grade Serous Ovarian Cancer by MeRIP Sequencing

“…IHC staining was performed using a previously described protocol. 31 , 32 The staining intensity was evaluated as follows: 0, no staining; 1, beige; 2, darker beige; and 3, tan. The staining extent was scored as follows: 0, 0% stained; 1, 1% to 25% stained; 2, 26% to 50% stained; and 3, 51% to 100% stained.…”

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

“…For instance, higher KDM6A and KDM6B expression is reportedly associated with greater H3K27me3 demethylation in human OS tissue and different OS cell lines 16 . In another study that examined IHC-stained OS tissue samples from 53 patients, higher KDM4B levels were positively associated with shorter OS survival as well as OS progression, as determined by higher Enneking staging results, a higher likelihood of distant metastases and poor differentiation on histology 24 . KDM4C silencing has been shown to increase H3K9me3 levels in MG63 and SaOS-2 human OS cells 25 .…”

“…Hypoxic environments occur in many solid tumors, including OS, and can trigger the release of hypoxia-inducible factors HIF-1α, HIF-2α, and HIF-3α, which modulate EMT master regulators such as SNAIL and TWIST to promote EMT and CSC progression 26 27 28 . In OS, HIF-3α overexpression in hypoxic conditions can activate KDM3A to decrease H3K9me2 levels at the SOX9 mRNA promoter region, leading to greater OS proliferation and invasion while restricting apoptosis 26 , while another study has found that higher levels of KDM4B and HIF-1α are associated with worse OS prognosis and progression to metastatic disease 24 .…”

Targeting ferroptosis in osteosarcoma

“…Lysine demethylase 4 (KDM4) subfamily H3K9 histone demethylases, as epigenetic regulators, are mainly responsible for the demethylation of histones H3K9 and H3K36 to influence chromosome structure and modulate gene expression [49] , resulting in a pivotal function in cell differentiation, development and death, and are involved in the study of diverse cancer prognosis and mechanisms including OS [50] , [51] . Chen et al clarified that deletion of KDM4A induced ferroptosis in OS cells by applying different forms of cell death inhibitors.…”