Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature
Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/193 |
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| author | Georgios Tsakonas Andreas Koulouris Dominika Kazmierczak Johan Botling Cristian Ortiz-Villalon Helena Nord Magnus Lindskog Martin Sandelin Patrick Micke Per Hydbring Simon Ekman |
| author_facet | Georgios Tsakonas Andreas Koulouris Dominika Kazmierczak Johan Botling Cristian Ortiz-Villalon Helena Nord Magnus Lindskog Martin Sandelin Patrick Micke Per Hydbring Simon Ekman |
| author_sort | Georgios Tsakonas |
| collection | DOAJ |
| description | Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections. |
| first_indexed | 2024-03-09T03:32:01Z |
| format | Article |
| id | doaj.art-fb33ffee24294bdaa3b0b604b2213efa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:32:01Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fb33ffee24294bdaa3b0b604b2213efa2023-12-03T14:54:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124119310.3390/ijms24010193Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA SignatureGeorgios Tsakonas0Andreas Koulouris1Dominika Kazmierczak2Johan Botling3Cristian Ortiz-Villalon4Helena Nord5Magnus Lindskog6Martin Sandelin7Patrick Micke8Per Hydbring9Simon Ekman10Thoracic Oncology Center, Karolinska University Hospital, 17176 Stockholm, SwedenThoracic Oncology Center, Karolinska University Hospital, 17176 Stockholm, SwedenDepartment of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 75105 Uppsala, SwedenDepartment of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, SwedenDepartment of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, 75105 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 75105 Uppsala, SwedenDepartment of Medical Sciences, Department of Oncology, University Hospital, Uppsala University, 75185 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 75105 Uppsala, SwedenDepartment of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, SwedenThoracic Oncology Center, Karolinska University Hospital, 17176 Stockholm, SwedenDistant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.https://www.mdpi.com/1422-0067/24/1/193non-small cell lung cancerbrain metastasismicroRNA |
| spellingShingle | Georgios Tsakonas Andreas Koulouris Dominika Kazmierczak Johan Botling Cristian Ortiz-Villalon Helena Nord Magnus Lindskog Martin Sandelin Patrick Micke Per Hydbring Simon Ekman Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature International Journal of Molecular Sciences non-small cell lung cancer brain metastasis microRNA |
| title | Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature |
| title_full | Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature |
| title_fullStr | Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature |
| title_full_unstemmed | Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature |
| title_short | Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature |
| title_sort | matched analyses of brain metastases versus primary non small cell lung cancer reveal a unique microrna signature |
| topic | non-small cell lung cancer brain metastasis microRNA |
| url | https://www.mdpi.com/1422-0067/24/1/193 |
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