Wan Zunmin, Li Xiaohong, Sun Jinghua, Li Xiaohua, Liu Zhongzhen, Dong Haojian, Zhou Qing, Qiu Hailong, Xu Jinjin, Yang Tingyu, Wang Wen-Jing, Ou Yanqiu
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Cardiovasc Med. 2022 May 31;9:892000. doi: 10.3389/fcvm.2022.892000. eCollection 2022.
The lack of accessible noninvasive tools to examine the molecular alterations limits our understanding of the causes of total anomalous pulmonary venous connection (TAPVC), as well as the identification of effective operational strategies. Here, we consecutively enrolled peripheral leukocyte transcripts of 26 preoperative obstructive and 22 non-obstructive patients with TAPVC. Two-hundred and fifty six differentially expressed mRNA and 27 differentially expressed long noncoding RNA transcripts were dysregulated. The up-regulated mRNA was enriched in the hydrogen peroxide catabolic process, response to mechanical stimulus, neutrophil degranulation, hemostasis, response to bacterium, and the NABA CORE MATRISOME pathway, all of which are associated with the development of fibrosis. Furthermore, we constructed predictive models using multiple machine-learning algorithms and tested the performance in the validation set. The mRNA and lncRNA were screened based on multiple iterations. The random forest prediction model can predict preoperative obstruction patients in the validation set with high accuracy (area under curve = 1; sensitivity = 1). These data highlight the potential of peripheral leukocyte transcripts to evaluate obstructive-related pathophysiological alterations, leading to precision healthcare solutions that could improve patient survival after surgery. It also provides a novel direction for the study of preoperative obstructive TAPVC.
缺乏可用于检查分子改变的非侵入性工具限制了我们对完全性肺静脉异位连接（TAPVC）病因的理解，以及有效手术策略的确定。在此，我们连续纳入了26例术前阻塞性和22例非阻塞性TAPVC患者的外周血白细胞转录本。256个差异表达的mRNA和27个差异表达的长链非编码RNA转录本表达失调。上调的mRNA在过氧化氢分解代谢过程、对机械刺激的反应、中性粒细胞脱颗粒、止血、对细菌的反应以及NABA核心基质体途径中富集，所有这些都与纤维化的发展有关。此外，我们使用多种机器学习算法构建了预测模型，并在验证集中测试了其性能。基于多次迭代筛选出mRNA和lncRNA。随机森林预测模型能够在验证集中高精度地预测术前阻塞性患者（曲线下面积=1；敏感性=1）。这些数据突出了外周血白细胞转录本在评估阻塞相关病理生理改变方面的潜力，从而带来可改善患者术后生存率的精准医疗解决方案。它还为术前阻塞性TAPVC的研究提供了一个新方向。
