慢性血栓栓塞性肺动脉高压研究：12个候选基因收敛至 FOS 与 CD163 两个候选标志物
一项11月14日发表于《科学报告》的研究联合分析单细胞与整体 RNA 测序数据，寻找与吞噬调节因子相关的慢性血栓栓塞性肺动脉高压候选诊断标志物。该病以机化血栓物质与持续性肺动脉高压为特征。
数据方面，研究使用了一个机构内部队列，包括8名慢性血栓栓塞性肺动脉高压患者与8名慢性血栓栓塞性肺病患者，并结合一个公共单细胞 RNA 测序数据集。在单细胞数据解析出的细胞群中，单核吞噬细胞的吞噬相关基因集活性较高。
筛选路径上，研究把差异表达基因与单核吞噬细胞相关模块基因取交集，得到12个候选基因；再经三种机器学习方法与受试者工作特征分析筛选，最终保留 FOS 与 CD163 两个候选标志物，两者在患者中均呈下调。由两基因构建的列线图在训练队列中显示出初步区分能力。
功能分析显示，两基因共同富集于血小板活化与中性粒细胞脱颗粒通路；CD163 与 B 细胞呈正相关。计算预测的化合物 CID:71,703,489 被预测可与两个标志物结合，其中 CD163 复合物在模拟中更稳定。研究还用逆转录定量 PCR 在独立队列中验证了两基因表达下降。
作者来自河北医科大学第二医院呼吸与危重症医学科，研究获河北省自然科学基金资助。作者强调，相关结果为计算推断，仍需实验与细胞类型特异性验证。
CTEPH Biomarker Study Narrows 12 Candidate Genes to FOS and CD163 as Candidate Diagnostic Markers
A study published November 14 in Scientific Reports jointly analysed single-cell and bulk RNA sequencing data to identify candidate diagnostic biomarkers associated with phagocytic regulatory factors in chronic thromboembolic pulmonary hypertension, a progressive pulmonary vascular disorder marked by organized thrombotic material and persistent pulmonary hypertension.
The team used an in-house bulk RNA-sequencing cohort of eight patients with CTEPH and eight with chronic thromboembolic pulmonary disease, together with a public single-cell RNA sequencing dataset. Among the resolved cell populations, mononuclear phagocytes showed high activity of the phagocytosis-related gene set.
Overlapping differentially expressed genes with mononuclear phagocyte-associated module genes yielded 12 candidates. Screening with three machine learning methods and receiver operating characteristic analysis retained FOS and CD163 as candidate diagnostic biomarkers, both downregulated in CTEPH. A two-gene nomogram showed preliminary discrimination in the training cohort.
The two biomarkers shared enrichment in platelet activation and neutrophil degranulation pathways, while CD163 was positively correlated with B cells. Compound CID:71,703,489 was predicted computationally to bind both biomarkers, and the simulated CD163 complex was more stable than the FOS complex. Reduced expression of both biomarkers was further supported by RT-qPCR in an independent cohort.
The authors are affiliated with the Second Hospital of Hebei Medical University, and the work was supported by the Natural Science Foundation of Hebei Province. The authors state that the findings are computational inferences and require experimental and cell-type-specific validation.
来源：Scientific Reports
发布：GSM·美国（发布链接）
图片来源：图：肺栓塞后右心室扩张的胸部 CT 影像。来源：Solomonbgh，Wikimedia Commons，CC0。 / Photo: Chest CT image showing right ventricular dilatation after pulmonary embolism. Source: Solomonbgh, Wikimedia Commons, CC0.
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