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Regions were selected from FFPE tumor slides for transcriptomic and proteomic analysis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How strong was the correspondence between proteomics and transcriptomics?",{"text":117,"@type":113},"The correlation was modest, with an average Pearson r of 0.43 at the gene level.",{"name":119,"@type":110,"acceptedAnswer":120},"Which type of heterogeneity was more pronounced, between tumors or within the same tumor?",{"text":121,"@type":113},"Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue showed distinct molecular characteristics.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},405916,1790862168,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Article  \nSpatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter-and Intratumoral Heterogeneity  \nBe¡ta Szeitz 1, Tibor Glasz 2, Zolt¡n Herold 1, G¡bor Tâth 3, Mirjam Balbisi 3,4, J¡nos Fillinger 5, Szabolcs Horv¡th 5, R²ka Moh¡csi 1, Ho Jeong Kwon 6, Judit Moldvay 7, Lilla Turi¡k 3,4 and Attila Marcell Sz¡sz 1,8,9, *  \nCitation: Szeitz, B.; Glasz, T.; Herold, Z.; Tóth, G.; Balbisi, M.; Fillinger, J.; Horváth, S.; Mohácsi, R.; Kwon, H.J.; Moldvay, J.; et al. Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter-and Intratumoral Heterogeneity. Int. J. Mol. Sci. 2023, 24, 11369. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241411369  \nAcademic Editor: Barbara Ruaro  \nReceived: 9 June 2023  \nRevised: 28 June 2023  \nAccepted: 4 July 2023  \nPublished: 12 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; [szeitz.beata@phd.semmelweis.hu](szeitz.beata@phd.semmelweis.hu) (B.S.)  \n2 Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary  \n3 MS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, 1117 Budapest, Hungary  \n4 Doctoral School of Pharmaceutical Sciences, Semmelweis University, 1085 Budapest, Hungary  \n5 Department of Pathology, National Kor¡nyi Institute of Pulmonology, 1121 Budapest, Hungary  \n6 Department of Biotechnology, Division of Life Sciences, Yonsei University, Seoul 03722, Republic of Korea  \n7 1st Department of Pulmonology, National Kor¡nyi Institute of Pulmonology, 1121 Budapest, Hungary  \n8 Department of Tumor Biology, National Kor¡nyi Institute of Pulmonology, 1121 Budapest, Hungary  \n9 Department of Bioinformatics, Semmelweis University, 1094 Budapest, Hungary  \n* Correspondence: [szasz.attila_marcell@med.semmelweis-univ.hu](szasz.attila_marcell@med.semmelweis-univ.hu); Tel.: +36-1-459-1500  \nAbstract: Pulmonary adenocarcinomas (pADCs) with an ALK rearrangement are a rare cancer subtype, necessitating comprehensive molecular investigations to unravel their heterogeneity and improve therapeutic strategies. In this pilot study, we employed spatial transcriptomic (NanoString GeoMx) and proteomic profiling to investigate seven treatment-naïve pADCs with an ALK rearrangement. On each FFPE tumor slide, 12 smaller and 2–6 larger histopathologically annotated regions were selected for transcriptomic and proteomic analysis, respectively. The correlation between proteomics and transcriptomics was modest (average Pearson's r = 0.43 at the gene level) . Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue exhibited distinct molecular characteristics. We identified potential markers and dysregulated pathways associated with tumors, with a varying extent of immune infiltration, as well as with mucin and stroma content. Notably, some markers appeared to be specific to the ALK-driven subset of pADCs. Our data showed that within tumors, elements of the extracellular matrix, including FN1, exhibited substantial variability. Additionally, we mapped the co-localization patterns of tumor microenvironment elements. This study represents the first spatially resolved profiling of ALK-driven pADCs at both the gene and protein expression levels. Our findings may contribute to a better understanding of this cancer type prior to treatment","cbCair55L4MSdIZw","https://ap.wps.com/l/cbCair55L4MSdIZw","pdf",2883912,21,"English","# Abstract\n# Introduction\n## Lung cancer background and histological subtypes\n## Molecular subtypes and ALK-driven adenocarcinoma","[{\"question\":\"What methods were used to profile ALK-rearranged pulmonary adenocarcinomas spatially?\",\"answer\":\"The study combined spatial transcriptomic profiling using NanoString GeoMx with proteomic profiling. Regions were selected from FFPE tumor slides for transcriptomic and proteomic analysis.\"},{\"question\":\"How strong was the correspondence between proteomics and transcriptomics?\",\"answer\":\"The correlation was modest, with an average Pearson r of 0.43 at the gene level.\"},{\"question\":\"Which type of heterogeneity was more pronounced, between tumors or within the same tumor?\",\"answer\":\"Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue showed distinct molecular characteristics.\"}]","Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter-and Intratumoral Heterogeneity | PDF",1790562526,53]