Intracranial metastases

Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expressions in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs.

Materials and methods: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR.

Results: Differential analysis identified 373 miRNAs with a significantly different expressions between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p, and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expressions of selected miRNAs in 5 BM groups as well as their diagnostic potential.

These is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature 1).

A retrospective case series including patients who underwent resection of cranial metastases from March 2014 to April 2021 at a single center. This identified 112 patients who underwent 124 resections. The median age was 65 years old (24-84) and the most frequent primary cancers were nonsmall cell lung cancer (56%), breast adenocarcinoma (13%), melanoma (6%), and colorectal adenocarcinoma (6%). Postoperative MRI with contrast was performed within 48 hours in 56% of patients and radiation treatment was administered in 41%. GraphPad Prism 9.2.0 was used for the survival analysis.

At the time of data collection, 23% were still alive with a median follow-up of 1070 days (68-2484). The 30- and 90-day, and 1- and 5-year overall survival rates were 93%, 83%, 35%, and 17%, respectively. The most common causes of death within 90 days were as follows: unknown (32%), systemic or intracranial disease progression (26%), and pneumonia (21%). Age and extent of neurosurgical resection were associated with overall survival (P < 0.05). Patients aged >70 had a median survival of 5.4 months compared with 9.7, 11.4, and 11.4 for patients <50, 50-59, and 60-69, respectively. Gross-total resection achieved an overall survival of 11.8 months whereas the sub-total, debulking, and unclear extent of resection led to a median survival of 5.7, 7.0, and 9.0 months, respectively.

Age and extent of resection are potential predictors of long-term survival 2).

Roskova I, Vecera M, Radova L, Trachtova K, Siegl F, Hermanova M, Hendrych M, Kren L, Vybihal V, Valekova H, Kasparova P, Kolouskova I, Kazda T, Slaby O, Jancalek R, Sana J, Smrcka M. Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin. Cancer Genomics Proteomics. 2023 Jan-Feb;20(1):18-29. doi: 10.21873/cgp.20361. PMID: 36581345.
Henderson D, Zafar A, Bjornson A, Razak A, Achawal S, Danciut M, Smith A, O'Reilly G, Rajaraman C, Bahl A. Prognostic factors following resection of intracranial metastases. Surg Neurol Int. 2022 May 27;13:219. doi: 10.25259/SNI_103_2022. PMID: 35673669; PMCID: PMC9168344.
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