BACKGROUND Currently, the diagnosis of achalasia mainly relies on invasive or radioactive examinations. This study aimed to develop a noninvasive diagnostic method for achalasia based on specific serum markers. METHODS Serum levels of profilin-1, galectin-10, immunoglobulin heavy variable (IGHV) 3-9, vasodilator-stimulated phosphoprotein (VASP) and transgelin-2 were measured in achalasia patients and controls by enzyme linked immunosorbent assay. The diagnostic values and thresholds were determined by the receiver operating characteristic curve analysis. Then, dysphagia patients were prospectively enrolled to validate the ability of these molecules for achalasia diagnosing. RESULTS 142 achalasia patients and 50 non-achalasia controls (healthy volunteers (HVs) and reflux esophagitis (RE) patients) were retrospectively included. The serum levels of profilin-1, galectin-10 and transgelin-2 in achalasia patients were significantly higher than those in HVs and RE patients (p all < 0.001). Profilin-1, galectin-10 and transgelin-2 were of good performance in diagnosing achalasia, with optimal thresholds of 2171.2 pg/ml, 33.9 pg/ml and 1630.6 pg/ml, respectively. Secondly, 40 dysphagia patients were prospectively enrolled to the validation of achalasia. For profilin-1, the positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were 100.0%, 64.5%, 45.0% and 100.0% respectively. The figures for transgelin-2 were 65.5%, 90.9%, 95.0% and 50.0%. When both increased, the PPV reached to 100.0%. When both indexes were normal, the NPV was 100.0%. CONCLUSIONS Profilin-1 and transgelin-2 were promising biomarkers for achalasia diagnosis, and performed better in combination. Further multicenter studies are necessary to verify their application as preliminary screening tools for achalasia.

中文翻译：

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血清标记物作为贲门失弛缓症无创诊断方法的开发和验证。

背景技术目前贲门失弛缓症的诊断主要依靠侵入性或放射性检查。本研究旨在开发一种基于特异性血清标志物的贲门失弛缓症的无创诊断方法。方法通过酶联免疫吸附试验测定贲门失弛缓症患者和对照者的血清中profilin-1、galectin-10、免疫球蛋白重链(IGHV) 3-9、血管舒张刺激磷蛋白(VASP)和transgelin-2水平。通过受试者工作特征曲线分析确定诊断值和阈值。然后，前瞻性地招募吞咽困难患者来验证这些分子诊断贲门失弛缓症的能力。结果 回顾性纳入 142 名贲门失弛缓症患者和 50 名非贲门失弛缓症对照者（健康志愿者 (HV) 和反流性食管炎 (RE) 患者）。贲门失弛缓症患者的血清profilin-1、galectin-10和transgelin-2水平显着高于HV和RE患者（p均<0.001）。Profilin-1、galectin-10 和 transgelin-2 在诊断贲门失弛缓症方面表现良好，最佳阈值分别为 2171.2 pg/ml、33.9 pg/ml 和 1630.6 pg/ml。其次，前瞻性招募了 40 名吞咽困难患者来验证贲门失弛缓症。Profilin-1的阳性预测值（PPV）、阴性预测值（NPV）、敏感性和特异性分别为100.0%、64.5%、45.0%和100.0%。transgelin-2 的数字分别为 65.5%、90.9%、95.0% 和 50.0%。当两者都增加时，PPV达到100.0%。当两项指标均正常时，NPV为100.0%。结论 Profilin-1 和 transgelin-2 是贲门失弛缓症诊断的有前途的生物标志物，并且联合使用效果更好。需要进一步的多中心研究来验证其作为贲门失弛缓症初步筛查工具的应用。