Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature

Georgios Tsakonas; Andreas Koulouris; Dominika Kazmierczak; Johan Botling; Cristian Ortiz-Villalon; Helena Nord; Magnus Lindskog; Martin Sandelin; Patrick Micke; Per Hydbring; Simon Ekman

doi:10.3390/ijms24010193

Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature

Int J Mol Sci. 2022 Dec 22;24(1):193. doi: 10.3390/ijms24010193.

Authors

Affiliations

¹ Thoracic Oncology Center, Karolinska University Hospital, 17176 Stockholm, Sweden.
² Department of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, Sweden.
³ Department of Immunology, Genetics and Pathology, Uppsala University, 75105 Uppsala, Sweden.
⁴ Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, 75105 Uppsala, Sweden.
⁵ Department of Pelvic Cancer, Genitourinary Oncology Unit, Karolinska University Hospital, 17176 Stockholm, Sweden.
⁶ Department of Medical Sciences, Department of Oncology, University Hospital, Uppsala University, 75185 Uppsala, Sweden.

Abstract

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.

Keywords: brain metastasis; microRNA; non-small cell lung cancer.

MeSH terms

Brain Neoplasms* / genetics
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / pathology
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
MicroRNAs* / metabolism

Substances

MicroRNAs
Mirn129 microRNA, human

Grants and funding

This research was funded by the European Society for Medical Oncology (A.K.), the Hellenic Society of Medical Oncology (A.K.), the Stockholm Cancer Society, Sweden, grant number 174093 (S.E.), the Lion Cancer Fund in Uppsala, Sweden (S.E.), the Sjöberg Foundation, Sweden (S.E.), and the Swedish Research Council, grant number 2019-01711 (P.H.).