Liu Hailun, Chen Chen, Fehm Tanja, Cheng Zhongping, Neubauer Hans
Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Universitaetsstr, 1, 40225 Duesseldorf, Germany.
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Diagnostics (Basel). 2022 Feb 12;12(2):470. doi: 10.3390/diagnostics12020470.
Ovarian cancer (OC) is characterized by late-stage presentation, chemoresistance, and poor survival. Evaluating the prognosis of OC patients via effective biomarkers is essential to manage OC progression and to improve survival; however, it has been barely established. Here, we intend to identify differentially expressed genes (DEGs) as potential prognostic biomarkers of OC via bioinformatic analyses. Initially, a total of thirteen DEGs were extracted from different public databases as candidates. The expression of KIF20A, one of the DEGs, was correlated with a worse outcome of OC patients. The functional correlation of the DEGs with mitosis and the prognostic value of KIF20A imply a high correlation between mitotic kinesins (KIFs) and OC development. Finally, we found that KIF20A, together with the other nine mitotic KIFs (4A, 11, 14, 15, 18A, 18B, 23, C1, and2C) were upregulated and activated in OC tissues. Among the ten, seven overexpressed mitotic KIFs (11, 14, 18B, 20A, 23, and C1) were correlated with unfavorable clinical prognosis. Moreover, KIF20A and KIF23 overexpression was associated with worse prognosis in OC patients treated with platinum/taxol chemotherapy, while OCs overexpressing mitotic KIFs (11, 15, 18B, and C1) were resistant to MAPK pathway inhibitors. In conclusion, worse outcomes of OC patients were correlated with overexpression of several mitotic KIFs, which may serve both as prognostic biomarkers and therapeutic targets for OC.
卵巢癌(OC)的特征是出现较晚、具有化学抗性且生存率低。通过有效的生物标志物评估OC患者的预后对于控制OC进展和提高生存率至关重要;然而,这一点尚未得到充分确立。在此,我们打算通过生物信息学分析来鉴定差异表达基因(DEGs)作为OC潜在的预后生物标志物。最初,从不同的公共数据库中总共提取了13个DEGs作为候选基因。其中一个DEG,即KIF20A的表达与OC患者较差的预后相关。DEGs与有丝分裂的功能相关性以及KIF20A的预后价值意味着有丝分裂驱动蛋白(KIFs)与OC发展之间存在高度相关性。最后,我们发现KIF20A与其他九个有丝分裂KIFs(4A、11、14、15、18A、18B、23、C1和2C)在OC组织中上调并被激活。在这十个基因中,七个过表达的有丝分裂KIFs(11、14、18B、20A、23和C1)与不良临床预后相关。此外,KIF20A和KIF23的过表达与接受铂/紫杉醇化疗的OC患者较差的预后相关,而过表达有丝分裂KIFs(11、15、18B和C1)的OC对MAPK通路抑制剂具有抗性。总之,OC患者较差的预后与几种有丝分裂KIFs的过表达相关,这些KIFs可能既是OC的预后生物标志物,也是治疗靶点。