Division of Pulmonary and Critical Care Medicine, Virginia Commonwealth University Medical Center, Richmond, VA, United States of America.
Department of Pediatrics, University of California San Diego School of Medicine, San Diego, CA, United States of America.
PLoS One. 2020 May 8;15(5):e0232181. doi: 10.1371/journal.pone.0232181. eCollection 2020.
There is ongoing research into the development of novel molecular markers that may complement fluid cytology malignant pleural effusion (MPE) diagnosis. In this exploratory pilot study, we hypothesized that there are distinct differences in the pleural fluid microbiome profile of malignant and non-malignant pleural diseases.
From a prospectively enrolled pleural fluid biorepository, samples of MPE were included. Non-MPE effusion were included as comparators. 16S rRNA gene V4 region amplicon sequencing was performed. Exact Sequence Variants (ESVs) were used for diversity analyses. The Shannon and Richness indices of alpha diversity and UniFrac beta diversity measures were tested for significance using permutational multivariate analysis of variance. Analyses of Composition of Microbiome was used to identify differentially abundant bacterial ESVs between the groups controlled for multiple hypothesis testing.
38 patients with MPE and 9 with non-MPE were included. A subgroup of patients with metastatic adenocarcinoma histology were identified among MPE group (adenocarcinoma of lung origin (LA-MPE) = 11, breast origin (BA-MPE) = 11). MPE presented with significantly greater alpha diversity compared to non-MPE group. Within the MPE group, BA-MPE was more diverse compared to LA-MPE group. In multivariable analysis, ESVs belonging to family S24-7 and genera Allobaculum, Stenotrophomonas, and Epulopiscium were significantly enriched in the malignant group compared to the non-malignant group.
Our results are the first to demonstrate a microbiome signature according to MPE and non-MPE. The role of microbiome in pleural effusion pathogenesis needs further exploration.
目前正在研究新的分子标志物,这些标志物可能有助于补充液体细胞学恶性胸腔积液(MPE)的诊断。在这项探索性的初步研究中,我们假设恶性和非恶性胸膜疾病的胸腔液微生物组谱存在明显差异。
从一个前瞻性胸腔液生物库中纳入 MPE 样本。将非 MPE 渗出液作为对照纳入。进行 16S rRNA 基因 V4 区扩增子测序。使用精确序列变异(ESV)进行多样性分析。使用置换多元方差分析检验 alpha 多样性和 UniFrac β多样性度量的 Shannon 和丰富度指数的显著性。使用微生物组组成分析来识别组间差异丰富的细菌 ESV,同时控制多重假设检验。
纳入 38 例 MPE 患者和 9 例非 MPE 患者。在 MPE 组中鉴定出一组转移性腺癌组织学患者(肺来源的腺癌(LA-MPE)= 11 例,乳腺来源的腺癌(BA-MPE)= 11 例)。与非 MPE 组相比,MPE 的 alpha 多样性显著增加。在 MPE 组中,BA-MPE 比 LA-MPE 组的多样性更大。在多变量分析中,属于 S24-7 科和 Allobaculum、Stenotrophomonas 和 Epulopiscium 属的 ESV 在恶性组中明显比非恶性组丰富。
我们的研究结果首次证明了根据 MPE 和非 MPE 的微生物组特征。微生物组在胸腔积液发病机制中的作用需要进一步探索。