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      <comment>Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [KH130356, KKP126790, 2020-1.1.6-JOVo, TKP2021-EGA-33, FK-143751, KTIA_NAP_13-2014-0021, NAP2-2017-1.2.1-NKP-00002, K129065, KNN121510]; Austrian Science Fund [FWF I3522, FWF I3977, FWF I4677]; New National Excellence Program of the Ministry for Innovation and Technology of Hungary [UNKP-20-3, UNKP-21-3]; Hungarian Respiratory Society (MPA) [2020]; ILCF Young Investigator Grant; Bolyai Research Scholarship of the Hungarian Academy of Sciences; New National Excellence Program of the Minis-try for Innovation and Technology [UNKP-19-4]; Royal Physiographic Society of Lund; Mrs. Berta Kamprad's Cancer Foundation [FBKS-2020-22- (291)]; Brazilian foundation CAPES [CAPES 88887.130697]; Netherlands X-omics Initiative (NWO) [184.034.019]
            Funding text: This work was supported by the Hungarian National Research, Development and Innovation Office [grant numbers KH130356, KKP126790 to BD; 2020-1.1.6-JOVo} , TKP2021-EGA-33 and FK-143751 to BD and ZM; KTIA_NAP_13-2014-0021, NAP2-2017-1.2.1-NKP-00002 to J Mo and ZS; K129065 to J Mo; KNN121510 to AMS) . BD was also supported by the Austrian Science Fund [grant numbers FWF I3522, FWF I3977, FWF I4677) . ZM was supported by the UNKP-20-3 and UNKP-21-3 New National Excellence Program of the Ministry for Innovation and Technology of Hungary, and by the Hungarian Respiratory Society (MPA #2020) . ZM is recipient of the ILCF Young Investigator Grant. VL is a recipient of the Bolyai Research Scholarship of the Hungarian Academy of Sciences and the UNKP-19-4 New National Excellence Program of the Minis-try for Innovation and Technology. MR acknowledges funding from the Royal Physiographic Society of Lund and the Mrs. Berta Kamprad?s Cancer Foundation [grant number FBKS-2020-22- (291) ] . We thank the Brazilian foundation CAPES for the scholarship to NW [grant number CAPES 88887.130697] . PH was supported by the Netherlands X-omics Initiative (NWO, project number 184.034.019) .</comment>
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      <title>Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases</title>
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Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases.

Materials and methods
Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259.

Results
Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases.

Conclusions
This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.</abstractText>
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																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10026954&quot; target=&quot;_blank&quot;&gt;Bagó A G
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Bagó Attila György&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Idegsebészet&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;Országos Klinikai Idegtudományi Intézet&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10068108&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10068108&quot; target=&quot;_blank&quot;&gt;Szállási Z
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Szállási Zoltán&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Onkológia, daganatkutatás&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;&lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Intézet&quot;&gt;I&lt;/span&gt;/Patológiai, Igazságügyi és Biztosítási Orvostani Intézet&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10003072&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10003072&quot; target=&quot;_blank&quot;&gt;Moldvay J
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Moldvay Judit&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Tüdõgyógyászat&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;&lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Intézet&quot;&gt;I&lt;/span&gt;/&lt;span title=&quot;Patológiai, Igazságügyi és Biztosítási Orvostani Intézet&quot;&gt;PIBOI&lt;/span&gt;/KTIA_NAP_13 Agymetasztázis kutatócsoport; &lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Intézet&quot;&gt;I&lt;/span&gt;/Patológiai, Igazságügyi és Biztosítási Orvostani Intézet&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10023803&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10023803&quot; target=&quot;_blank&quot;&gt;Szász A M
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Szász Attila Marcell&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; emlőpatologia&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;&lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Intézet&quot;&gt;I&lt;/span&gt;/Bioinformatika Tanszék&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Malm J
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Horvatovich P
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Pizzatti L
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Domont G B
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10034324&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10034324&quot; target=&quot;_blank&quot;&gt;Rényi-Vámos F
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Rényi-Vámos Ferenc István&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Mellkassebész&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;Országos Onkológiai Intézet; &lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Klinikum&quot;&gt;K&lt;/span&gt;/Mellkassebészeti Klinika&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Hoetzenecker K
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Hoda M A
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Marko-Varga G
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Schelch K
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10071898&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10071898&quot; target=&quot;_blank&quot;&gt;Megyesfalvi Z
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Megyesfalvi Zsolt&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Orvostudomány&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;Országos Onkológiai Intézet; &lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Klinikum&quot;&gt;K&lt;/span&gt;/Mellkassebészeti Klinika&lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; &gt;Rezeli M&lt;sup&gt;**&lt;/sup&gt; ✉
    &lt;/span&gt;
;&amp;nbsp;&amp;nbsp;&amp;nbsp;
							&lt;span class=&quot;author-name&quot; mtid=&quot;10000046&quot;&gt;&lt;a 
																				   href=&quot;/gui2/?type=authors&amp;mode=browse&amp;sel=10000046&quot; target=&quot;_blank&quot;&gt;Döme B ✉
            (&lt;span class=&quot;authorship-author-name&quot;&gt;Döme Balázs&lt;/span&gt;
            &lt;span class=&quot;authorAux-mtmt&quot;&gt; Tumor indukált angiogenezis&lt;/span&gt;)
			&lt;/a&gt;
    &lt;/span&gt;
&lt;span class=&quot;author-affil&quot;&gt;Országos Onkológiai Intézet; &lt;span title=&quot;Semmelweis Egyetem&quot;&gt;SE&lt;/span&gt;/&lt;span title=&quot;Általános Orvostudományi Kar&quot;&gt;AOK&lt;/span&gt;/&lt;span title=&quot;Klinikum&quot;&gt;K&lt;/span&gt;/Mellkassebészeti Klinika; Országos Korányi Pulmonológiai Intézet&lt;/span&gt;

				    &lt;/div&gt;
&lt;/div&gt;
&lt;div class=&quot;title&quot;&gt;&lt;a href=&quot;/gui2/?mode=browse&amp;params=publication;33364842&quot; target=&quot;_blank&quot;&gt;Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases&lt;/a&gt;&lt;/div&gt;    &lt;div&gt;		&lt;span class=&quot;journal-title&quot;&gt;ESMO OPEN&lt;/span&gt;

        &lt;span class=&quot;journal-issn&quot;&gt;(&lt;a target=&quot;_blank&quot; href=&quot;https://portal.issn.org/resource/ISSN/2059-7029&quot;&gt;2059-7029&lt;/a&gt; &lt;a target=&quot;_blank&quot; href=&quot;https://portal.issn.org/resource/ISSN/2059-7029&quot;&gt;2059-7029&lt;/a&gt;)&lt;/span&gt;:
		&lt;span class=&quot;journal-volume&quot;&gt;8&lt;/span&gt; &lt;span class=&quot;journal-issue&quot;&gt;1&lt;/span&gt;
&lt;span class=&quot;page&quot;&gt;
		Paper 100741.
	 13 p. 
&lt;/span&gt;		 &lt;span class=&quot;year&quot;&gt;(2023)&lt;/span&gt;  
    &lt;/div&gt;
&lt;div class=&quot;pub-footer&quot;&gt;
    

	&lt;span class=&quot;language&quot; xmlns=&quot;http://www.w3.org/1999/html&quot;&gt;Nyelv:
			Angol
		 |  &lt;/span&gt;

	&lt;span class=&quot;identifiers&quot;&gt;
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&quot;&gt;
							
							&lt;a style=&quot;color:blue&quot; title=&quot;10.1016/j.esmoop.2022.100741&quot; target=&quot;_blank&quot; href=&quot;https://doi.org/10.1016/j.esmoop.2022.100741&quot;&gt;
									DOI
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							&lt;a style=&quot;color:blue&quot; title=&quot;000901873400002&quot; target=&quot;_blank&quot; href=&quot;https://www.webofscience.com/wos/woscc/full-record/000901873400002&quot;&gt;
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	&lt;OnlyViewableByAuthor&gt;&lt;div class=&quot;ratings&quot;&gt;
				&lt;div class=&quot;journal-subject&quot;&gt;Folyóirat szakterülete: Scopus - Cancer Research&amp;nbsp;&amp;nbsp;&amp;nbsp;SJR indikátor:&amp;nbsp;Q1&lt;/div&gt;
				&lt;div class=&quot;journal-subject&quot;&gt;Folyóirat szakterülete: Scopus - Oncology&amp;nbsp;&amp;nbsp;&amp;nbsp;SJR indikátor:&amp;nbsp;Q1&lt;/div&gt;
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	&lt;div class=&quot;publication-citation&quot; style=&quot;margin-left: 0.5cm;&quot;&gt;
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		| Független: 13
		| Függő: 1
		| Nem jelölt: 0
		| WoS jelölt: 14 
		|  Scopus jelölt:&amp;nbsp;13 
		|  WoS/Scopus jelölt:&amp;nbsp;14 
		|  DOI jelölt:&amp;nbsp;14 
		
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		&lt;a target=&quot;_blank&quot; href=&quot;/api/publication?cond=citations.related;eq;33364842&amp;sort=publishedYear,desc&amp;sort=title&quot;&gt;
			Idézett közlemények száma: 2
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    &lt;div class=&quot;mtid&quot;&gt;&lt;span class=&quot;long-pub-mtid&quot;&gt;Közlemény: 33364842&lt;/span&gt;
    | &lt;span class=&quot;status-data status-VALIDATED&quot;&gt; 	Egyeztetett
  &lt;/span&gt;
        
	
	
Forrás	 Idéző
	
	
    | &lt;span class=&quot;type-subtype&quot;&gt;Folyóiratcikk
			( Szakcikk
			
			)
		&lt;/span&gt;
      		| &lt;span class=&quot;pub-category&quot;&gt;Tudományos&lt;/span&gt;
	| &lt;span class=&quot;publication-sourceOfData&quot;&gt;kézi felvitel&lt;/span&gt;
&lt;/div&gt;

&lt;div class=&quot;funder&quot;&gt; (KH130356),    (KKP126790),    (2020-1.1.6-JOVO),    (TKP2021-EGA-33),    (FK-143751),    (KTIA_NAP_13-2014-0021),    (NAP2-2017-1.2.1-NKP-00002),    (K129065),    (KNN121510),    (ÚNKP-20-3),    (UNKP-21-3),    (Hungarian Respiratory Society),    (János Bolyai Research Scholarship),    ITM ÚNKP(UNKP-19-4)   &lt;/div&gt;
&lt;div class=&quot;lastModified&quot;&gt;Utolsó módosítás: 2026.01.06. 09:30 Wolf György (MTMT Központi admin)
&lt;/div&gt;


        &lt;div class=&quot;lockedBy&quot;&gt;Központi kezelésű 2023.10.04. 09:54  Kovács Marcell (MTMT Közp., admin)
        &lt;/div&gt;


	&lt;pre class=&quot;comment&quot; style=&quot;margin-top: 0; margin-bottom: 0;&quot;&gt;&lt;u&gt;Megjegyzés&lt;/u&gt;: Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [KH130356, KKP126790, 2020-1.1.6-JOVo, TKP2021-EGA-33, FK-143751, KTIA_NAP_13-2014-0021, NAP2-2017-1.2.1-NKP-00002, K129065, KNN121510]; Austrian Science Fund [FWF I3522, FWF I3977, FWF I4677]; New National Excellence Program of the Ministry for Innovation and Technology of Hungary [UNKP-20-3, UNKP-2...&lt;/pre&gt;
&lt;/div&gt;&lt;/div&gt;</template2>
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