Leng Qixin, Holden Van K, Deepak Janaki, Todd Nevins W, Jiang Feng
Department of Pathology, School of Medicine, University of Maryland, 10 S. Pine St., Baltimore, MD 21201, USA.
Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Diagnostics (Basel). 2021 Feb 27;11(3):407. doi: 10.3390/diagnostics11030407.
Non-small cell lung cancer (NSCLC) is the number one cancer killer and its early detection can reduce mortality. Accumulating evidences suggest an etiopathogenic role of microorganisms in lung tumorigenesis. Certain bacteria are found to be associated with NSCLC. Herein we evaluated the potential use of microbiome as biomarkers for the early detection of NSCLC. We used droplet digital PCR to analyze 25 NSCLC-associated bacterial genera in 31 lung tumor and the paired noncancerous lung tissues and sputum of 17 NSCLC patients and ten cancer-free smokers. Of the bacterial genera, four had altered abundances in lung tumor tissues, while five were aberrantly abundant in sputum of NSCLC patients compared with their normal counterparts (all < 0.05). Acidovorax and Veillonella were further developed as a panel of sputum biomarkers that could diagnose lung squamous cell carcinoma (SCC) with 80% sensitivity and 89% specificity. The use of Capnocytophaga as a sputum biomarker identified lung adenocarcinoma (AC) with 72% sensitivity and 85% specificity. The use of Acidovorax as a sputum biomarker had 63% sensitivity and 96% specificity for distinguishing between SCC and AC, the two major types of NSCLC. The sputum biomarkers were further validated for the diagnostic values in a different cohort of 69 NSCLC cases and 79 cancer-free controls. Sputum microbiome might provide noninvasive biomarkers for the early detection and classification of NSCLC.
非小细胞肺癌（NSCLC）是头号癌症杀手，其早期检测可降低死亡率。越来越多的证据表明微生物在肺癌发生过程中具有病因学作用。已发现某些细菌与NSCLC有关。在此，我们评估了微生物组作为NSCLC早期检测生物标志物的潜在用途。我们使用液滴数字PCR分析了31例肺肿瘤以及17例NSCLC患者和10名无癌吸烟者的配对非癌肺组织及痰液中的25种与NSCLC相关的细菌属。在这些细菌属中，有4种在肺肿瘤组织中的丰度发生了改变，而与正常对照相比，有5种在NSCLC患者的痰液中异常丰富（均P<0.05）。嗜酸菌属和韦荣球菌属进一步被开发为一组痰液生物标志物，可诊断肺鳞状细胞癌（SCC），敏感性为80%，特异性为89%。使用二氧化碳嗜纤维菌作为痰液生物标志物诊断肺腺癌（AC）的敏感性为72%，特异性为85%。使用嗜酸菌属作为痰液生物标志物区分SCC和AC这两种主要类型的NSCLC，敏感性为63%，特异性为96%。在另一组由69例NSCLC病例和79名无癌对照组成的队列中，进一步验证了痰液生物标志物的诊断价值。痰液微生物组可能为NSCLC的早期检测和分类提供非侵入性生物标志物。
