Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity
Pulmonary adenocarcinomas (pADCs) with an <i>ALK</i> 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)...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11369 |
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| author | Beáta Szeitz Tibor Glasz Zoltán Herold Gábor Tóth Mirjam Balbisi János Fillinger Szabolcs Horváth Réka Mohácsi Ho Jeong Kwon Judit Moldvay Lilla Turiák Attila Marcell Szász |
| author_facet | Beáta Szeitz Tibor Glasz Zoltán Herold Gábor Tóth Mirjam Balbisi János Fillinger Szabolcs Horváth Réka Mohácsi Ho Jeong Kwon Judit Moldvay Lilla Turiák Attila Marcell Szász |
| author_sort | Beáta Szeitz |
| collection | DOAJ |
| description | Pulmonary adenocarcinomas (pADCs) with an <i>ALK</i> 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 <i>ALK</i> 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 <i>r</i> = 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 <i>FN1</i>, 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 with ALK inhibitors. |
| first_indexed | 2024-03-11T01:00:53Z |
| format | Article |
| id | doaj.art-a1673b734ab74f30aa97c9863fe4f8a2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:00:53Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a1673b734ab74f30aa97c9863fe4f8a22023-11-18T19:38:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141136910.3390/ijms241411369Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral HeterogeneityBeáta Szeitz0Tibor Glasz1Zoltán Herold2Gábor Tóth3Mirjam Balbisi4János Fillinger5Szabolcs Horváth6Réka Mohácsi7Ho Jeong Kwon8Judit Moldvay9Lilla Turiák10Attila Marcell Szász11Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, HungaryDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryMS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, 1117 Budapest, HungaryMS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, 1117 Budapest, HungaryDepartment of Pathology, National Korányi Institute of Pulmonology, 1121 Budapest, HungaryDepartment of Pathology, National Korányi Institute of Pulmonology, 1121 Budapest, HungaryDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryDepartment of Biotechnology, Division of Life Sciences, Yonsei University, Seoul 03722, Republic of Korea1st Department of Pulmonology, National Korányi Institute of Pulmonology, 1121 Budapest, HungaryMS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, 1117 Budapest, HungaryDivision of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, HungaryPulmonary adenocarcinomas (pADCs) with an <i>ALK</i> 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 <i>ALK</i> 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 <i>r</i> = 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 <i>FN1</i>, 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 with ALK inhibitors.https://www.mdpi.com/1422-0067/24/14/11369lung adenocarcinomapulmonary adenocarcinoma<i>ALK</i> rearrangementmulti-omicsdigital spatial profilingproteomics |
| spellingShingle | Beáta Szeitz Tibor Glasz Zoltán Herold Gábor Tóth Mirjam Balbisi János Fillinger Szabolcs Horváth Réka Mohácsi Ho Jeong Kwon Judit Moldvay Lilla Turiák Attila Marcell Szász Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity International Journal of Molecular Sciences lung adenocarcinoma pulmonary adenocarcinoma <i>ALK</i> rearrangement multi-omics digital spatial profiling proteomics |
| title | Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity |
| title_full | Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity |
| title_fullStr | Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity |
| title_full_unstemmed | Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity |
| title_short | Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity |
| title_sort | spatially resolved proteomic and transcriptomic profiling of anaplastic lymphoma kinase rearranged pulmonary adenocarcinomas reveals key players in inter and intratumoral heterogeneity |
| topic | lung adenocarcinoma pulmonary adenocarcinoma <i>ALK</i> rearrangement multi-omics digital spatial profiling proteomics |
| url | https://www.mdpi.com/1422-0067/24/14/11369 |
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