Fanjie Meng, Hao Li, Ruoyi Jin, Airong Yang, Hao Luo, Xiao Li, Peiyu Wang, Yaxing Zhao, Olga Chervova, Kaicheng Tang, Sida Cheng, Bin Hu, Yun Li, Jianpeng Sheng, Fan Yang, David Carbone, Kezhong Chen, Jun Wang
{"title":"与肺腺癌淋巴结转移相关的空间免疫基因组模式","authors":"Fanjie Meng, Hao Li, Ruoyi Jin, Airong Yang, Hao Luo, Xiao Li, Peiyu Wang, Yaxing Zhao, Olga Chervova, Kaicheng Tang, Sida Cheng, Bin Hu, Yun Li, Jianpeng Sheng, Fan Yang, David Carbone, Kezhong Chen, Jun Wang","doi":"10.1186/s40164-024-00574-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD.</p><p><strong>Methods: </strong>We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently.</p><p><strong>Results: </strong>Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p < 0.05), compared to LN negative tumors. Furthermore, we developed a novel predictive model for LN metastasis likelihood, designed to inform non-surgical treatment strategies, optimize personalized therapy plans, and potentially improve outcomes for patients who are ineligible for surgery.</p><p><strong>Conclusions: </strong>This study offers a comprehensive analysis of the genetic and immune profiles in LUAD primary tumors with LN metastasis, identifying key immunogenomic patterns linked to metastatic progression. The predictive model derived from these insights marks a substantial advancement in personalized treatment, underscoring its potential to improve patient management.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514955/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma.\",\"authors\":\"Fanjie Meng, Hao Li, Ruoyi Jin, Airong Yang, Hao Luo, Xiao Li, Peiyu Wang, Yaxing Zhao, Olga Chervova, Kaicheng Tang, Sida Cheng, Bin Hu, Yun Li, Jianpeng Sheng, Fan Yang, David Carbone, Kezhong Chen, Jun Wang\",\"doi\":\"10.1186/s40164-024-00574-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD.</p><p><strong>Methods: </strong>We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently.</p><p><strong>Results: </strong>Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p < 0.05), compared to LN negative tumors. Furthermore, we developed a novel predictive model for LN metastasis likelihood, designed to inform non-surgical treatment strategies, optimize personalized therapy plans, and potentially improve outcomes for patients who are ineligible for surgery.</p><p><strong>Conclusions: </strong>This study offers a comprehensive analysis of the genetic and immune profiles in LUAD primary tumors with LN metastasis, identifying key immunogenomic patterns linked to metastatic progression. The predictive model derived from these insights marks a substantial advancement in personalized treatment, underscoring its potential to improve patient management.</p>\",\"PeriodicalId\":12180,\"journal\":{\"name\":\"Experimental Hematology & Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.4000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514955/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Hematology & Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40164-024-00574-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40164-024-00574-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma.
Background: Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD.
Methods: We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently.
Results: Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p < 0.05), compared to LN negative tumors. Furthermore, we developed a novel predictive model for LN metastasis likelihood, designed to inform non-surgical treatment strategies, optimize personalized therapy plans, and potentially improve outcomes for patients who are ineligible for surgery.
Conclusions: This study offers a comprehensive analysis of the genetic and immune profiles in LUAD primary tumors with LN metastasis, identifying key immunogenomic patterns linked to metastatic progression. The predictive model derived from these insights marks a substantial advancement in personalized treatment, underscoring its potential to improve patient management.
期刊介绍：
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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