Wang Fei, Wang Zi-Ran, Ding Xue-Song, Yang Hua, Guo Ye, Su Hao, Wan Xi-Run, Wang Li-Juan, Jiang Xiang-Yang, Xu Yan-Hua, Chen Feng, Cui Wei, Feng Feng-Zhi
Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Oncol. 2022 Oct 21;12:982806. doi: 10.3389/fonc.2022.982806. eCollection 2022.
Gestational trophoblastic neoplasia (GTN) is a group of clinically rare tumors that develop in the uterus from placental tissue. Currently, its satisfactory curability derives from the timely and accurately classification and refined management for patients. This study aimed to discover biomarkers that could predict the outcomes of GTN patients after first-line chemotherapy.
A total of 65 GTN patients were included in the study. Patients were divided into the good or poor outcome group and the clinical characteristics of the patients in the two groups were compared. Furthermore, the serum peptide profiles of all patients were uncovered by using weak cation exchange magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Feature peaks were identified by three machine learning algorithms and then models were constructed and compared using five machine learning methods. Additionally, liquid chromatography mass spectrometry was used to identify the feature peptides.
Multivariate logistic regression analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) risk score was associated with poor outcomes. Eight feature peaks ( =1287, 2042, 2862, 2932, 2950, 3240, 3277 and 6626) were selected for model construction and validation by the three algorithms. Based on the panel combining FIGO risk score and peptide serum signatures, the neural network (nnet) model showed promising performance in both the training (AUC=0.9635) and validation (AUC=0.8788) cohorts. Peaks at 2042, 2862, 2932, 3240 were identified as the partial sequences of transthyretin, fibrinogen alpha chain (FGA), beta-globin and FGA, respectively.
We combined FIGO risk score and serum peptide signatures using the nnet method to construct the model which can accurately predict outcome of GTN patients after first-line chemotherapy. With this model, patients can be further classified and managed, and those with poor predicted outcomes can be given more attention for developing treatment failure.
妊娠滋养细胞肿瘤(GTN)是一组临床上罕见的肿瘤,起源于子宫内的胎盘组织。目前,其令人满意的治愈率源于对患者的及时、准确分类以及精细化管理。本研究旨在发现能够预测GTN患者一线化疗后结局的生物标志物。
本研究共纳入65例GTN患者。将患者分为预后良好或不良组,并比较两组患者的临床特征。此外,使用弱阳离子交换磁珠和基质辅助激光解吸/电离飞行时间质谱法揭示所有患者的血清肽谱。通过三种机器学习算法识别特征峰,然后使用五种机器学习方法构建并比较模型。另外,采用液相色谱质谱法鉴定特征肽。
多因素逻辑回归分析显示,国际妇产科联盟(FIGO)风险评分与不良预后相关。通过三种算法选择了8个特征峰(m/z = 1287、2042、2862、2932、2950、3240、3277和6626)用于模型构建和验证。基于FIGO风险评分和肽血清特征的组合,神经网络(nnet)模型在训练队列(AUC = 0.9635)和验证队列(AUC = 0.8788)中均表现出良好的性能。m/z 2042、2862、2932、3240处的峰分别被鉴定为转甲状腺素蛋白、纤维蛋白原α链(FGA)、β-珠蛋白和FGA的部分序列。
我们使用nnet方法将FIGO风险评分和血清肽特征相结合构建模型,该模型能够准确预测GTN患者一线化疗后的结局。借助此模型,患者可得到进一步分类和管理,对于预测结局不良的患者,可在治疗失败发生时给予更多关注。