Overexpression of JARID1B is associated with poor prognosis and chemotherapy resistance in epithelial ovarian cancer

Abstract

JARID1B, a histone demethylase, has been reported to be highly expressed in various human cancers. In the present study, we investigated the association of JARID1B level with epithelial ovarian cancer (EOC) and prognosis of patients with EOC. We analyzed JARID1B expression in 20 normal ovaries, 20 benign ovarian tumor (BOT) samples, and 45 epithelial ovarian carcinoma specimens by quantitative PCR (qRT-PCR) and western blotting analyses. JARID1B was further examined in 120 EOC specimens from patients with different histological stages via immunohistochemistry. Possible correlations between JARID1B levels and prognosis as well as chemotherapy resistance of EOC patients were determined by univariate and multivariate analyses. JARID1B level was significantly increased in EOC, as compared to normal ovaries and BOT. Among 120 EOC cases examined, the 5-year progression-free survival (PFS) rates were 17 and 85 % in patients with high and low JARID1B expression, respectively (hazard ratio = 17.85, 95 % confidence interval (CI) 6.31–50.51, P < 0.001). Similarly, the 5-year overall survival (OS) rates for patients with high and low JARID1B expression were 28 and 92 % respectively (hazard ratio = 21.8, 95 % CI 5.92–71.81, P < 0.001). Positive correlation between JARID1B level and chemotherapy resistance was observed in patients with EOC (odds ratio (OR) 36.81, 95 % CI 4.84–280.11, P < 0.001). JARID1B could serve as an important biomarker for prognosis and chemotherapy resistance of EOC patients.

Histone demethylase lysine demethylase 5B in development and cancer

“…KDM5B overexpression could also predict proliferation properties in head and neck squamous cell carcinoma and KDM5B knockdown resulted in G1 arrest and early apoptosis by suppressing Bcl-2 family members [80]. Similar results were observed in esophageal squamous cell carcinoma [81, 82], colorectal cancer [35], epithelial ovarian cancer(EOC) [83], cervical cancer, renal cell carcinoma [72], diffuse large B-cell lymphoma [84] and other leukemic cells lines [85]. KDM5B was up-regulated in multiple typed of leukemia and related to aberrant cell proliferation.…”

JARID1 Histone Demethylases: Emerging Targets in Cancer

“…JARID1B amplification and overexpression are strongly associated with poor prognosis in hormone receptor-positive tumors and drive a luminal-type gene expression profile [4]. It is also upregulated in numerous other cancers including prostate [5], hepatocellular [6], and ovarian [7]. Despite low JARID1B levels in melanomas relative to benign nevi [8], these cancers contain a fraction of cells where high JARID1B expression confers stem cell-like molecular and functional traits [9], drives oxidative metabolism, and increases drug resistance [10].…”

KDM5 demethylases and their role in cancer cell chemoresistance

“…The KDM5B level was significantly increased in EOC, as compared to normal ovaries and benign ovarian tumor. A positive correlation between KDM5B level and chemotherapy resistance was observed in patients with EOC, thus KDM5B could serve as an important biomarker for prognosis and chemoresistance of EOC patients . KDM5B is essential in luminal cell‐specific gene expression programs and it is an oncogene in luminal breast cancer.…”

“…KDM5B has been identified as an oncogene in many cancers e.g. neuroblastoma, bladder, lung, prostate, ovarian and breast carcinoma . Its increased levels together with the elevated expression of long noncoding RNA (lncRNA), MALAT1, suggests a functional association in progression and metastasis formation in triple negative breast cancer (TNBC).…”

“…neuroblastoma, bladder, lung, prostate, ovarian and breast carcinoma. 32,[35][36][37][38][39] Its increased levels together with the elevated expression of long noncoding RNA (lncRNA), MALAT1, suggests a functional association in progression and metastasis formation in triple negative breast cancer (TNBC). Hsa-miR-448 has been shown to be a negative regulator of MALAT1 and to disrupt KDM5B-MALAT1 signaling axis in TNBC cells.…”