Jun-Chieh J Tsay, Fares Darawshy, Chan Wang, Benjamin Kwok, Kendrew K Wong, Benjamin G Wu, Imran Sulaiman, Hua Zhou, Bradley Isaacs, Matthias C Kugler, Elizabeth Sanchez, Alexander Bain, Yonghua Li, Rosemary Schluger, Alena Lukovnikova, Destiny Collazo, Yaa Kyeremateng, Ray Pillai, Miao Chang, Qingsheng Li, Rami S Vanguri, Anton S Becker, William H Moore, George Thurston, Terry Gordon, Andre L Moreira, Chandra M Goparaju, Daniel H Sterman, Aristotelis Tsirigos, Huilin Li, Leopoldo N Segal, Harvey I Pass
{"title":"预测早期腺癌预后的肺部微生物和宿主基因组特征","authors":"Jun-Chieh J Tsay, Fares Darawshy, Chan Wang, Benjamin Kwok, Kendrew K Wong, Benjamin G Wu, Imran Sulaiman, Hua Zhou, Bradley Isaacs, Matthias C Kugler, Elizabeth Sanchez, Alexander Bain, Yonghua Li, Rosemary Schluger, Alena Lukovnikova, Destiny Collazo, Yaa Kyeremateng, Ray Pillai, Miao Chang, Qingsheng Li, Rami S Vanguri, Anton S Becker, William H Moore, George Thurston, Terry Gordon, Andre L Moreira, Chandra M Goparaju, Daniel H Sterman, Aristotelis Tsirigos, Huilin Li, Leopoldo N Segal, Harvey I Pass","doi":"10.1158/1055-9965.EPI-24-0661","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.</p><p><strong>Methods: </strong>In 91 early-stage (Stage IA/IB) LUAD-patients 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.</p><p><strong>Results: </strong>23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD 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 with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways.</p><p><strong>Conclusions: </strong>Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83).</p><p><strong>Impact: </strong>This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma.\",\"authors\":\"Jun-Chieh J Tsay, Fares Darawshy, Chan Wang, Benjamin Kwok, Kendrew K Wong, Benjamin G Wu, Imran Sulaiman, Hua Zhou, Bradley Isaacs, Matthias C Kugler, Elizabeth Sanchez, Alexander Bain, Yonghua Li, Rosemary Schluger, Alena Lukovnikova, Destiny Collazo, Yaa Kyeremateng, Ray Pillai, Miao Chang, Qingsheng Li, Rami S Vanguri, Anton S Becker, William H Moore, George Thurston, Terry Gordon, Andre L Moreira, Chandra M Goparaju, Daniel H Sterman, Aristotelis Tsirigos, Huilin Li, Leopoldo N Segal, Harvey I Pass\",\"doi\":\"10.1158/1055-9965.EPI-24-0661\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.</p><p><strong>Methods: </strong>In 91 early-stage (Stage IA/IB) LUAD-patients 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.</p><p><strong>Results: </strong>23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD 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 with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. 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Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma.
Background: Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.
Methods: In 91 early-stage (Stage IA/IB) LUAD-patients 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.
Results: 23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD 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 with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways.
Conclusions: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83).
Impact: This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.
期刊介绍:
Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.