整合WNT/β-连环蛋白信号通路的列线图用于预测皮肤黑色素瘤的生存率

Nomogram Incorporating the WNT/β-Catenin Signaling Pathway for Predicting the Survival of Cutaneous Melanoma.

作者信息

Zhou Yu-Xin, Wang Xin, Pang De-Quan, Wang Ying-Man, Bai Jing, Tian Fei, Han Duo, Shi Shuwei, Hu Lei

机构信息

Department of Radiation Oncology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, People's Republic of China.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention & Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China.

出版信息

Int J Gen Med. 2021 Jun 23;14:2751-2761. doi: 10.2147/IJGM.S309616. eCollection 2021.

DOI:10.2147/IJGM.S309616

PMID:34188529

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8236283/

Abstract

BACKGROUND

Accurate prediction of the survival of cutaneous melanoma (CM) permits the selection of the optimal treatment. Currently, the TNM stage has limitations in predicting the survival of CM. There is evidence that the WNT/β-catenin signaling pathway has the potential to predict the CM prognosis. However, it still needs further investigation.

OBJECTIVE

This study aims to establish a nomogram incorporating the WNT/β-catenin signaling pathway to improve the predicted accuracy of the overall survival (OS) of CM.

METHODS

Two hundred and eighty CM patients were recruited and followed up. The clinicopathological characteristics and the key genes of the WNT/β-catenin signaling pathway (VEGF, β-catenin, and DKK1) were chosen as potential variables associated with the OS. In the training cohort (n = 190), a nomogram was built to estimate the 1-, 3-, and 5-year OS, and its discriminations and calibrations were valid by the verification cohort (n = 90). The predicted accuracies of the nomogram with or without the Wnt/β-catenin pathway and TNM stage were compared.

RESULTS

A nomogram integrating independent risk factors (ulceration, lymph node metastasis, distant metastasis, Breslow thickness, dermal mitoses, β-catenin, VEGF, and DKK1), which were evaluated by a multivariate analysis, was constructed to predict the 1-, 3-, and 5-year OS of CM patients. Good discrimination and calibration were obtained regardless of the training or validation datasets. The nomogram incorporating the Wnt/β-catenin signaling pathway showed the highest accuracy [area under the curve (AUC)=0.914, 0.852, 0.785] compared with the nomogram without the Wnt/β-catenin signaling pathway (AUC=0.693, 0.640, 0.615) and the TNM stage (AUC=0.726, 0.693, 0.673).

CONCLUSION

The prognostic value of the established nomogram incorporating the WNT/β-catenin signaling pathway was better than it without WNT/β-catenin signaling pathway and TNM stage, which might be beneficial in the development of optimal treatment options.

摘要

背景

准确预测皮肤黑色素瘤（CM）的生存期有助于选择最佳治疗方案。目前，TNM分期在预测CM生存期方面存在局限性。有证据表明，WNT/β-连环蛋白信号通路有预测CM预后的潜力。然而，仍需进一步研究。

目的

本研究旨在建立一个纳入WNT/β-连环蛋白信号通路的列线图，以提高CM总生存期（OS）的预测准确性。

方法

招募280例CM患者并进行随访。选择临床病理特征及WNT/β-连环蛋白信号通路的关键基因（VEGF、β-连环蛋白和DKK1）作为与OS相关的潜在变量。在训练队列（n = 190）中构建列线图以估计1年、3年和5年OS，并通过验证队列（n = 90）验证其区分度和校准度。比较有无Wnt/β-连环蛋白通路及TNM分期的列线图的预测准确性。

结果

通过多变量分析评估，构建了一个整合独立危险因素（溃疡、淋巴结转移、远处转移、Breslow厚度、真皮有丝分裂、β-连环蛋白、VEGF和DKK1）的列线图，用于预测CM患者的1年、3年和5年OS。无论训练数据集还是验证数据集，均获得了良好的区分度和校准度。与未纳入Wnt/β-连环蛋白信号通路的列线图（曲线下面积[AUC]=0.693、0.640、0.615）和TNM分期（AUC=0.726、0.693、0.673）相比，纳入Wnt/β-连环蛋白信号通路的列线图显示出最高的准确性（AUC=0.914、0.852、0.785）。