Zhu Mengna, Sun Si, Huang Lin, Gao Lingling, Chen Mengqing, Cai Jing, Wang Zehua, Peng Minggang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Histol Histopathol. 2025 Jan;40(1):73-87. doi: 10.14670/HH-18-761. Epub 2024 May 14.
The biological function of p27 largely depends on its subcellular localization and phosphorylation status. Different subcellular localizations and phosphorylation statuses of p27 may represent distinct clinical values, which are unclear in ovarian cancer. This study aimed to elucidate different subcellular localizations of p27 and pSer10p27 in predicting prognosis and chemotherapy response in ovarian cancer.
Meta-analyses were executed to evaluate the association of p27 and phosphorylated p27 with the prognosis of ovarian cancer patients. The expression levels and patterns of p27 and pSer10p27 were evaluated by immunohistochemistry. The correlations between different p27 states, clinicopathological features, and prognosis were analyzed. p27 and pSer10p27 expression levels in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines were detected using WB. KEGG analysis and WB were performed to evaluate the pathways in which p27 was involved.
Meta-analyses showed that p27 was associated with significantly better overall survival (OS) in ovarian cancer (HR=2.14; 95% CI [1.71-2.68]) and pSer10p27 was associated with significantly poor OS in mixed solid tumors (HR=2.56; 95% CI [1.76-3.73]). In our cohort of ovarian cancer patients, low total p27 remained independent risk factors of OS (HR=2.097; 95% CI [1.121-3.922], =0.021) and PFS (HR=2.483; 95% CI [1.364-4.518], =0.003), while low cytoplasmic pSer10p27 had independent protective effects in terms of OS (HR=0.472; 95% CI [0.248-0.898], =0.022) and PFS (HR=0.488; 95% CI [0.261-0.910], =0.024). Patients with low total p27/pSer10p27 and low nuclear p27 had worse chemotherapy responses, while patients with low cytoplasmic pSer10p27 expression had better chemotherapy responses. The protein levels of p27 and pSer10p27 were significantly reduced in the cisplatin-resistant cell lines SKOV3-cDDP and A2780-cDDP, and the level of p27/pSer10p27 was subjective to Akt activation.
The present study demonstrates that p27 and cytoplasmic pSer10p27 are promising biomarkers for predicting prognosis and chemotherapy response in ovarian cancer.
p27的生物学功能很大程度上取决于其亚细胞定位和磷酸化状态。p27不同的亚细胞定位和磷酸化状态可能代表不同的临床价值，这在卵巢癌中尚不清楚。本研究旨在阐明p27和pSer10p27的不同亚细胞定位在预测卵巢癌预后和化疗反应中的作用。
进行荟萃分析以评估p27和磷酸化p27与卵巢癌患者预后的相关性。通过免疫组织化学评估p27和pSer10p27的表达水平和模式。分析不同p27状态、临床病理特征和预后之间的相关性。使用蛋白质印迹法检测顺铂敏感和耐药卵巢癌细胞系中p27和pSer10p27的表达水平。进行KEGG分析和蛋白质印迹法以评估p27参与的信号通路。
荟萃分析表明，p27与卵巢癌患者显著更好的总生存期（OS）相关（HR=2.14；95%CI[1.71-2.68]），pSer10p27与混合实体瘤中显著较差的OS相关（HR=2.56；95%CI[1.76-3.73]）。在我们的卵巢癌患者队列中，低总p27仍然是OS（HR=2.097；95%CI[1.121-3.922]，P=0.021）和无进展生存期（PFS）（HR=2.483；95%CI[1.364-4.518]，P=0.003）的独立危险因素，而低细胞质pSer10p27在OS（HR=0.472；95%CI[0.248-0.898]，P=0.022）和PFS（HR=0.488；95%CI[0.261-0.910]，P=0.024）方面具有独立的保护作用。总p27/pSer10p27低和细胞核p27低的患者化疗反应较差，而细胞质pSer10p27表达低的患者化疗反应较好。在顺铂耐药细胞系SKOV3-cDDP和A2780-cDDP中，p27和pSer10p27的蛋白质水平显著降低，并且p27/pSer10p27的水平受Akt激活的影响。
本研究表明，p27和细胞质pSer10p27是预测卵巢癌预后和化疗反应的有前景的生物标志物。
