Division of Pulmonary, Critical Care and Sleep Medicine, NYU Grossman School of Medicine, NYU Langone Health, New York, New York.
Department of Medicine, NYU Grossman School of Medicine, NYU Langone Health, New York, New York.
Cancer Epidemiol Biomarkers Prev. 2024 Nov 1;33(11):1433-1444. doi: 10.1158/1055-9965.EPI-24-0661.
Risk of early-stage lung adenocarcinoma recurrence after surgical resection is significant, and the postrecurrence median survival is approximately 2 years. Currently, there are no commercially available biomarkers that predict recurrence. In this study, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.
In 91 patients with early-stage (stage IA/IB) lung adenocarcinoma with extensive follow-up, we used 16s rRNA gene sequencing and host RNA sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples.
Of 91 subjects, 23 had tumor recurrence over 5-year period. In tumor samples, lung adenocarcinoma recurrence was associated with enrichment in Dialister and Prevotella, whereas in unaffected lung samples, recurrence was associated with enrichment in Sphingomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with lung adenocarcinoma recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment in Stenotrophomonas geniculata and Chryseobacterium was positively correlated with upregulation of IL2, IL3, IL17, EGFR, and HIF1 signaling pathways among the host transcriptome. In tumor samples, enrichment in Veillonellaceae (Dialister), Ruminococcaceae, Haemophilus influenzae, and Neisseria was positively correlated with upregulation of IL1, IL6, IL17, IFN, and tryptophan metabolism pathways.
Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC = 0.83).
This study suggests that lung adenocarcinoma recurrence is associated with distinct pathophysiologic mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.
肺腺癌手术后早期复发的风险很大，复发后的中位生存时间约为 2 年。目前，尚无可预测复发的商业可用生物标志物。在本研究中，我们研究了肺部微生物和宿主基因组特征是否可以预测复发。
在 91 例有广泛随访的早期（IA/IB 期）肺腺癌患者中，我们使用 16s rRNA 基因测序和宿主 RNA 测序来绘制肿瘤和相邻未受影响的肺样本中的微生物和宿主转录组图谱。
在 91 名受试者中，有 23 名在 5 年内发生肿瘤复发。在肿瘤样本中，肺腺癌复发与 Dialister 和 Prevotella 的丰度增加有关，而在未受影响的肺样本中，复发与 Sphingomonas 和 Alloiococcus 的丰度增加有关。与肺腺癌复发相关的微生物和宿主基因组特征在未受影响的肺样本中的关联强度大于原发性肿瘤。在与复发相关的未受影响的肺样本中的微生物-宿主特征中，Stenotrophomonas geniculata 和 Chryseobacterium 的丰度增加与宿主转录组中 IL2、IL3、IL17、EGFR 和 HIF1 信号通路的上调呈正相关。在肿瘤样本中，Veillonellaceae（Dialister）、Ruminococcaceae、流感嗜血杆菌和奈瑟菌的丰度增加与 IL1、IL6、IL17、IFN 和色氨酸代谢途径的上调呈正相关。
总体而言，模型表明使用未受影响的肺样本进行微生物/转录组联合分析具有最佳的生物标志物性能（AUC = 0.83）。
这项研究表明，肺腺癌复发与未受影响的肺中微生物-宿主相互作用的独特病理生理机制有关，而与切除的肿瘤中存在的机制无关。
