Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, China.
Int J Mol Sci. 2023 Dec 20;25(1):109. doi: 10.3390/ijms25010109.
Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was examined by immunohistochemistry (IHC) staining of an ovarian tissue array (10 normal and 70 malignant samples). Drug sensitivity of ovarian cancer cell lines (including OVCAR3 and SKOV3) was measured by MTS assay. The modulation of MAPK15 expression in OVCAR3 and SKOV3 was verified by immunoblot and real-time PCR analyses. The prognostic value of MAPK15 in ovarian cancer patients was assessed using the Kaplan-Meier Plotter database and Gene Expression Omnibus (GEO) datasets. The IHC results showed that MAPK15 expression was negatively associated with tumor grade, TNM stage, tumor size, and regional lymph node metastasis of ovarian carcinoma. Importantly, overexpressing MAPK15 increased cisplatin toxicity in ovarian carcinoma cells and online database analysis indicated that patients with high MAPK15 expression had favorable prognosis with/without chemotherapy. Taken together, our results indicate that a decreased MAPK15 expression is associated with advanced-stage ovarian cancer and unfavorable survival outcomes. MAPK15 may be a new biomarker for ovarian cancer, and the encouraging therapeutic strategy would be found by combining the regulation of MAPK15 expression.
丝裂原活化蛋白激酶 15(MAPK15)已被报道与多种癌症有关。本研究旨在首次探讨 MAPK15 表达与卵巢癌进展/药物反应性的关系。为此,通过免疫组织化学(IHC)染色卵巢组织阵列(10 个正常和 70 个恶性样本)检测 MAPK15 表达水平。通过 MTS 测定法测量卵巢癌细胞系(包括 OVCAR3 和 SKOV3)的药物敏感性。通过免疫印迹和实时 PCR 分析验证了 MAPK15 在 OVCAR3 和 SKOV3 中的表达调节。使用 Kaplan-Meier Plotter 数据库和基因表达综合数据库(GEO)数据集评估了 MAPK15 在卵巢癌患者中的预后价值。IHC 结果表明,MAPK15 表达与卵巢癌的肿瘤分级、TNM 分期、肿瘤大小和局部淋巴结转移呈负相关。重要的是,过表达 MAPK15 增加了卵巢癌细胞中顺铂的毒性,并且在线数据库分析表明,高表达 MAPK15 的患者无论是否接受化疗,预后均较好。综上所述,我们的结果表明,MAPK15 表达降低与晚期卵巢癌和不良生存结局相关。MAPK15 可能是卵巢癌的一个新的生物标志物,通过调节 MAPK15 的表达可能会发现令人鼓舞的治疗策略。