Navi BB, Mathias R, Sherman CP, et al. - Since acute ischemic stroke (AIS) mechanisms can be distinguished by blood mRNA profiles, researchers tested the hypothesis that AIS related to cancer would have a distinctive profile of gene expression. Four groups of 10 individuals at 3 centers from 2009 to 2018 were prospectively recruited, and matched patients in AIS-only and cancer-only groups to patients in the cancer-stroke group by age, gender, and cancer type (if applicable). Individuals in the vascular risk factor group were matched to those in the cancer-stroke and stroke-only groups by age, gender, and vascular risk factors. The authors discovered that 50% of strokes were cryptogenic in the cancer-stroke group. Comparing the cancer-stroke group with the stroke-only group and taking into account cancer-only genes, 438 genes were expressed differently, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). The proof was provided in the blood mRNA expression profiles of patients with cancer-related AIS for a distinctive molecular signature. Future studies must determine whether blood mRNA can predict occult cancer detection in AIS individuals.