Expression and clinical significance of methyl‑CpG binding domain protein 2 in high‑grade serous ovarian cancer

Abstract

Platinum resistance is an important cause of clinical recurrence and mortality of patients with high-grade serous ovarian cancer (HGSOC). Methyl-CpG binding domain protein 2 (MBD2) serves an important role in tumor progression; however, its role in HGSOC remains unclear. The aim of the present study was to investigate the expression of MBD2 in HGSOC and its role in drug resistance and prognosis of HGSOC. MBD2 expression was analyzed by immunohistochemical staining and western blotting. The associations between MBD2 expression and clinical pathological features, platinum resistance and patient prognosis were analyzed using a χ 2 test, Kaplan-Meier analysis and Cox regression analysis. Positive MBD2 expression was detected in 73 (63.5%) of the HGSOC tissue samples, whereas it was undetectable in all 16 normal tissue samples (100%) analyzed, indicating a significantly higher expression level in tumor tissues compared with normal tissues (P<0.001). Additionally, MBD2 expression was significantly higher in platinum-resistant cases compared with that in platinum-sensitive cases (P<0.05). In addition, high expression of MBD2 was negatively associated with relapse-free survival (P<0.05). In conclusion, MBD2 was demonstrated to be a potential drug target and a biomarker for poor prognosis in HGSOC. WANGANG GONG 1-4 , MAOWEI NI 2-4 , ZHONGBO CHEN 2-4 and ZHIGUO ZHENG 2-4

Loss of MBD2 attenuates MLL-AF9-driven leukemogenesis by suppressing the leukemic cell cycle via CDKN1C

“…by binding to its promoter in leukemic cells Previous studies have shown that MBD2 functions as a "reader" of DNA methylation and translates methylated DNA into signals for transcriptional silencing [9,11,19,20]. Therefore, we reasoned that the transcript levels of CDKIs might be consequently restored after the loss of MBD2.…”

“…MBD2 also has cell-and tissue-specific functions that are context-dependent [8]. Many studies have demonstrated that MBD2 might bind to hypermethylated promoters of tumor suppressor genes and contribute to their transcriptional silencing in multiple tumors, such as ovarian cancer [9], renal cell carcinoma [10], and hepatocellular carcinoma [11]. Our previous study also showed that MBD2 acts as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL) lymphomagenesis in murine experiments [12].…”

Prolyl-4-Hydroxylase α Subunit 2 as a Novel Potential Biomarker for Predicting the Prognosis of Epithelial Ovarian Carcinoma

“…After positively stained cells count and background evaluation, semi-quantitative P4HA2 expression analysis by IHC was evaluated using a staining score, as Gong et al previously described. 12 The established staining score (range, 0–7) was the sum of staining intensity and proportion of positively stained cells. A final score of 0–4 points indicated no or low expression, and 5–7 points indicated high expression.…”

Epigenetic Regulation of Angiogenesis in Development and Tumors Progression: Potential Implications for Cancer Treatment

“…In ischemic insults, the essential endothelial genes such as eNOS and VEGFR 2 undergo a DNA methylation turnover, and MBD2 reads DNA methylation changes signals for mediating gene silencing ( Rao et al, 2011 ). MBD2 overexpression has been detected in various solid tumors and promotes cancer progression by mediating silencing of tumor suppressor genes ( Gong et al, 2020 ). MBD2 binds to the gene promoter of brain angiogenesis inhibitor 1 (BAI1) and inhibits its antiangiogenic and antitumorigenic properties in glioma cells.…”