S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension.
S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension.
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DOI：
10.1111/resp.13302
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Fares WH
中科院分区：
文献类型：
--
作者：
Tzouvelekis A;Herazo-Maya JD;Ryu C;Chu JH;Zhang Y;Gibson KF;Adonteng-Boateng PK;Li Q;Pan H;Cherry B;Ahmad F;Ford HJ;Herzog EL;Kaminski N;Fares WH
需要分子生物标志物来完善肺动脉高压（PH）患者的预后和表型分析。 S100A12 是各种炎症性疾病的新兴生物标志物。本研究旨在确定 S100A12 对 PH 的预后价值。对从特发性肺纤维化 (IPF) 患者收集的外周血单核细胞 (PBMC) 进行的探索性微阵列分析表明，S100A12 与 PH 和死亡率之间存在关联。因此，当前的研究旨在评估从另外两个中心的两个表型良好的 PH 队列中收集的外周血中 S100A12 之间的关联，以推导并验证 S100A12 蛋白血清浓度与死亡率之间的关联。发现和验证队列中的大多数患者属于世界卫生组织 (WHO) 第 1 组（肺动脉高压 (PAH)）或第 3 组（肺部疾病相关）肺动脉高压。在发现 PH 队列中，与对照组 (n = 22) 相比，PH 患者 (n = 51) 中的 S100A12 显着升高（29.8 vs 15.7 ng/mL，P < 0.001），并且与 PH 患者的心输出量呈负相关（r = -0.58，P < 0.001）。当汇总两个队列的 S100A12 数据时，与健康外部对照相比，PAH 和非 PAH PH 患者的 S100A12 较高（32.6、30.9、15.7 ng/mL；P < 0.001）。在发现组（n = 51；P = 0.008）和验证组（n = 40；P < 0.001）中，S100A12 与 PH 患者总体死亡率风险增加相关。 PH 患者中 S100A12 水平升高，并与死亡率增加相关。
Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH. Exploratory microarray analysis performed on peripheral blood mononuclear cells (PBMC) collected from idiopathic pulmonary fibrosis (IPF) patients suggested an association between S100A12 and both PH and mortality. So the current study was designed to evaluate for an association between S100A12 in peripheral blood collected from two well-phenotyped PH cohorts in two other centres to derive and validate an association between S100A12 protein serum concentrations and mortality. The majority of the patients in the discovery and validation cohorts were either World Health Organization (WHO) group 1 (pulmonary arterial hypertension (PAH)) or 3 (lung disease-associated) PH. In the discovery PH cohort, S100A12 was significantly increased in patients with PH (n = 51) compared to controls (n = 22) (29.8 vs 15.7 ng/mL, P < 0.001) and negatively correlated with cardiac output (r = −0.58, P < 0.001) in PH patients. When S100A12 data were pooled from both cohorts, PAH and non-PAH PH patients had higher S100A12 compared to healthy external controls (32.6, 30.9, 15.7 ng/mL; P < 0.001). S100A12 was associated with an increased risk in overall mortality in PH patients in both the discovery (n = 51; P = 0.008) and validation (n = 40; P < 0.001) cohorts. S100A12 levels are increased in PH patients and are associated with increased mortality.
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