Abstract
BackgroundThe incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death.MethodsWe executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization.ResultsWe discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference.ConclusionA multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease.
Highlights
There are approximately 180,000 new cases of brain metastases in the US each year [1]
We profiled global proteomes, genomes, and the metabolome of resected brain metastases from a number of tumor types. We provided both individual and integrated analyses that revealed brain metastasis with similar RNA expression provided different posttranscriptional and post-translational levels
Patients with treated with postoperative radiotherapy or placement of breast cancer patients treated with carmustine (BCNU)-containing wafers as previously described [17, 18]
Summary
There are approximately 180,000 new cases of brain metastases in the US each year [1]. Due to the heterogeneity in the presentation of these patients, several treatment options including surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT) have been adopted. There is the use of primary systemic targeted therapies for cancer that harbor actionable mutations like EGFR [9] or ALK [10]. In spite of these general guidelines, a large proportion of patients will fall into a category in which their brain metastases enumerate into an intermediate category between few and many, and for these patients, little prospective data exists [11]. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death
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