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Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871865, 81874036, 81972167]; Shanghai Education Development Foundation [16SG18]; Shanghai Municipal Education CommissionShanghai Municipal Education Commission (SHMEC) [16SG18]; Backbone Program of Shanghai Pulmonary Hospital [FKGG1802]; Shanghai Pujiang Talent Plan [2019PJD048]; Shanghai Key disciplines of Respiratory [2017ZZ02012]; University of Kansas Medical Center; Shanghai Sailing Program [20YF1407500]
Funding text: This study was supported in part by grants from the National Natural Science Foundation of China (No. 81871865, 81874036, and 81972167), "Shuguang Program" supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (No. 16SG18), the Backbone Program of Shanghai Pulmonary Hospital (No. FKGG1802), Shanghai Pujiang Talent Plan (No. 2019PJD048), and Shanghai Key disciplines of Respiratory (No. 2017ZZ02012), the start-up funds from the University of Kansas Medical Center (J.Z.), and the Shanghai Sailing Program (No. 20YF1407500).
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Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma
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Characterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8(+) T cell infiltration (P=0.048), and elevated CD4(+)Foxp3(+) T cell infiltration (P=0.036) and PD-1 expression (P=0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor - such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" > Jiang, Tao </span> <span class="author-type"> </span> ; <span class="author-name" > Yan, Yan </span> <span class="author-type"> </span> ; <span class="author-name" > Zhou, Kun </span> <span class="author-type"> </span> ; <span class="author-name" > Su, Chunxia </span> <span class="author-type"> </span> ; <span class="author-name" > Ren, Shengxiang </span> <span class="author-type"> </span> ; <span class="author-name" > Li, Nan </span> <span class="author-type"> </span> ; <span class="author-name" > Hou, Likun </span> <span class="author-type"> </span> ; <span class="author-name" > Guo, Xianchao </span> <span class="author-type"> </span> ; <span class="author-name" > Zhu, Wei </span> <span class="author-type"> </span> ; <span class="author-name" > Zhang, Henghui </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;32062157" mtid="32062157" target="_blank">Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma</a></div> <div class="pub-info"> <span class="journal-title">NPJ PRECISION ONCOLOGY</span> <span class="journal-volume">5</span> : <span class="journal-issue">1</span> <span class="page"> Paper: 6 , 9 p. </span> <span class="year">(2021)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1038/s41698-021-00151-w" target="_blank" href="https://doi.org/10.1038/s41698-021-00151-w"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000620239900002" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000620239900002"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85113678675" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85113678675"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="33580130" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33580130&dopt=Abstract"> PubMed </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:32062157 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core"> Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> </div> </div> </div><div class="JournalArticle Publication long-list">
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<div class="autype autype0"> <span class="author-name" >Jiang Tao
</span>
;
<span class="author-name" >Yan Yan
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;
<span class="author-name" >Zhou Kun
</span>
;
<span class="author-name" >Su Chunxia
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;
<span class="author-name" >Ren Shengxiang
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;
<span class="author-name" >Li Nan
</span>
;
<span class="author-name" >Hou Likun
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;
<span class="author-name" >Guo Xianchao
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;
<span class="author-name" >Zhu Wei
</span>
;
<span class="author-name" >Zhang Henghui
</span>
;
<span class="author-name" >Lin Jie ✉
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;
<span class="author-name" >Zhang Jun ✉
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;
<span class="author-name" >Zhou Caicun ✉
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;32062157" target="_blank">Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma</a></div> <div> <span class="journal-title">NPJ PRECISION ONCOLOGY</span>
<span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/2397-768X">2397-768X</a>)</span>:
<span class="journal-volume">5</span> <span class="journal-issue">1</span>
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Paper 6.
9 p.
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Idézett közlemények száma: 5
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<div class="mtid"><span class="long-pub-mtid">Közlemény: 32062157</span>
| <span class="status-data status-VALIDATED"> Egyeztetett
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<div class="lastModified">Utolsó módosítás: 2022.02.02. 14:33 Pirmann Tamás (OOI addmin5, admin)
</div>
<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871865, 81874036, 81972167]; Shanghai Education Development Foundation [16SG18]; Shanghai Municipal Education CommissionShanghai Municipal Education Commission (SHMEC) [16SG18]; Backbone Program of Shanghai Pulmonary Hospital [FKGG1802]; Shanghai Pujiang Talent Pla...</pre>
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