Abstract 3758: Tumor tissue and cerebrospinal fluid microRNA profiles enable the classification of brain metastasis accordingly to their origin

Abstract

Brain metastases (BMs) comprise a heterogeneous group of the most frequent intracranial tumors in adults, most originating in lung, breast, renal cell, and colorectal carcinomas and melanomas. Despite the recent improvements in imaging methodology resulting in earlier BM identification and advancements in treatment strategies, BMs are still a significant cause of patient morbidity. Furthermore, BMs frequency increases due to more prolonged survival of cancer patients and population aging. Since the most widely used prognostic scoring systems for BMs require prior knowledge of the primary origin and up to 14% of BMs are classified as BMs of unknown primary, there is an urgent unmet need for accurate biomarkers for identification of BM origin. MiRNAs are non-coding RNAs with an approximate length of 22 nucleotides, functioning as post-transcriptional regulators of gene expression. Dysregulated miRNA expression profile has been observed in many pathological processes, including the complex and not fully understood metastatic cascade. These molecules are very stable and present not only in tissues but also in human body fluids, including blood plasma and cerebrospinal fluid (CSF). Based on these facts, both tissue and circulating miRNAs are extensively studied as potential diagnostic biomarkers. Specific miRNA signatures of BMs were obtained using high-throughput miRNA profiling (Illumina small RNA sequencing) on 3 types of samples (metastatic tissue, blood plasma, CSF) from a cohort of 30 patients with BMs originating in the 5 tumor types – lung, breast, renal cell and colorectal carcinomas and melanomas (6 patients per group, 87 samples in total, only 3 CSF samples from RCC patients available). We identified significantly differentially expressed miRNAs in BM tissues with the ability to differentiate between primary origins. Tissue miRNAs could identify BMs originating from breast, colorectal and renal cell carcinomas and melanomas with high specificity and sensitivity. Interestingly, the heterogeneity of lung carcinomas was also characteristic for the corresponding BMs, making it challenging to distinguish accurately from other BMs. Even though the tissue-specific miRNA signature was the most precise, our results suggest a significant diagnostic potential of circulating miRNAs from CSF for BM patients. Therefore, these short and stable molecules could potentially help identify the origin of BMs of unknown primary. The research is supported by project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. Citation Format: Dagmar Al Tukmachi, Michaela Ruckova, Marek Vecera, Tana Machackova, Petra Pokorna, Marketa Hermanova, Michal Hendrych, Leos Kren, Ivana Roskova, Vaclav Vybihal, Hana Valekova, Radim Jancalek, Jiri Sana, Martin Smrcka, Ondrej Slaby. Tumor tissue and cerebrospinal fluid microRNA profiles enable the classification of brain metastasis accordingly to their origin. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3758.