Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings
Abstract Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM i...
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| Veröffentlicht in: | Carcinogenesis (New York) 2024-06, Vol.45 (6), p.387-398 |
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| creator | Yao, Meihong Chen, Hu Chen, Zui Wang, Yingying Shi, Dongliang Wu, Dan Li, Wen Huang, Jianping Chen, Guizhen Zheng, Qiaoling Ye, Zhengtao Zheng, Chenxin Yang, Yinghong |
| description | Abstract
Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P |
| doi_str_mv | 10.1093/carcin/bgae026 |
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Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.
The utilization of next-generation sequencing aided in the diagnosis of MPLCs from IM. Patients with higher expression of NECTIN4 or LILRB4 exhibited a poorer DFS. A more favorable response to immunotherapy may happen in MPLCs for having a more immune-activating microenvironment than IM.
Graphical Abstract
Graphical Abstract</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgae026</identifier><identifier>PMID: 38693810</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><ispartof>Carcinogenesis (New York), 2024-06, Vol.45 (6), p.387-398</ispartof><rights>The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c214t-949c4352a1dbff0e8d40efebb191c79e58e7d7ab11540d68d3c7a4bb1094c0323</cites><orcidid>0009-0000-6370-4150</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38693810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yao, Meihong</creatorcontrib><creatorcontrib>Chen, Hu</creatorcontrib><creatorcontrib>Chen, Zui</creatorcontrib><creatorcontrib>Wang, Yingying</creatorcontrib><creatorcontrib>Shi, Dongliang</creatorcontrib><creatorcontrib>Wu, Dan</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Huang, Jianping</creatorcontrib><creatorcontrib>Chen, Guizhen</creatorcontrib><creatorcontrib>Zheng, Qiaoling</creatorcontrib><creatorcontrib>Ye, Zhengtao</creatorcontrib><creatorcontrib>Zheng, Chenxin</creatorcontrib><creatorcontrib>Yang, Yinghong</creatorcontrib><title>Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Abstract
Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.
The utilization of next-generation sequencing aided in the diagnosis of MPLCs from IM. Patients with higher expression of NECTIN4 or LILRB4 exhibited a poorer DFS. A more favorable response to immunotherapy may happen in MPLCs for having a more immune-activating microenvironment than IM.
Graphical Abstract
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Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.
The utilization of next-generation sequencing aided in the diagnosis of MPLCs from IM. Patients with higher expression of NECTIN4 or LILRB4 exhibited a poorer DFS. A more favorable response to immunotherapy may happen in MPLCs for having a more immune-activating microenvironment than IM.
Graphical Abstract
Graphical Abstract</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>38693810</pmid><doi>10.1093/carcin/bgae026</doi><tpages>12</tpages><orcidid>https://orcid.org/0009-0000-6370-4150</orcidid></addata></record> |
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| title | Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings |
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