Juul Amanda, Arshad Arman, Christophersen Alice V, Larsen Julie Gellert, Pulga Alexis, Kristiansen Pernille, Rasmussen Torben Riis, Skaarup Søren Helbo, Hilberg Ole, Laursen Christian B
Odense Respiratory Research Unit (ODIN), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.
Eur Clin Respir J. 2025 Mar 7;12(1):2474277. doi: 10.1080/20018525.2025.2474277. eCollection 2025.
Small lung lesions can represent early-stage lung cancer but are difficult to diagnose. The bronchoscopic approach has the lowest risk of complications; however, the diagnostic yield is generally lower compared to trans-thoracic biopsies. Cell-free tumor DNA (cftDNA) is fragmented DNA stemming from a tumor. CftDNA in the form of methylated HOXA9 has previously been detected in bronchial lavage (BL) and has been proposed as an adjunct to conventional biopsies to improve diagnostic yield. The aim of this study was to assess whether methylated HOXA in BL could be utilized as an add-on diagnostic modality for bronchoscopic tissue sampling.
The study was conducted as a prospective diagnostic accuracy study in accordance with STARD guidelines. Patients undergoing bronchoscopy for diagnosing peripheral lung lesions were included. During bronchoscopy, BL samples were collected before and after biopsy. The samples were analyzed for methylated HOXA using a predefined cutoff and compared to histopathology or the result of CT surveillance.
One hundred seventy-two patients were included, with samples collected from 155 patients. A definite diagnosis was obtained from bronchoscopic biopsies in 47.1%. The sensitivity and specificity of methylated HOXA9 in BL were 68.0 (58.0-76.8) and 76.3 (59.8-88.6), respectively. The positive likelihood ratio of methylated HOXA9 in patients with a non-diagnostic biopsy was 2.11.
The diagnostic accuracy of methylated HOXA9 in BL was too low to confirm or refute malignancy following an inconclusive biopsy; however, BL was superior to blood samples.
肺部小结节可能代表早期肺癌，但难以诊断。支气管镜检查方法并发症风险最低；然而，与经胸活检相比，其诊断率通常较低。游离肿瘤DNA（cftDNA）是源自肿瘤的片段化DNA。甲基化HOXA9形式的cftDNA此前已在支气管灌洗（BL）中检测到，并被提议作为传统活检的辅助手段以提高诊断率。本研究的目的是评估BL中甲基化HOXA是否可作为支气管镜组织采样的附加诊断方式。
本研究按照STARD指南进行前瞻性诊断准确性研究。纳入因诊断周围型肺部病变而接受支气管镜检查的患者。在支气管镜检查期间，在活检前后采集BL样本。使用预定义的临界值分析样本中的甲基化HOXA，并与组织病理学或CT监测结果进行比较。
纳入172例患者，从155例患者中采集了样本。支气管镜活检确诊率为47.1%。BL中甲基化HOXA9的敏感性和特异性分别为68.0（58.0 - 76.8）和76.3（59.8 - 88.6）。活检未明确诊断的患者中甲基化HOXA9的阳性似然比为2.11。
BL中甲基化HOXA9的诊断准确性过低，无法在活检结果不明确后证实或排除恶性肿瘤；然而，BL优于血液样本。
