Distinctive mRNA Signatures May Prove Diagnostic for Cancer-Related AIS

A recently published paper described a distinctive molecular signature present in blood mRNA expression profiles of patients with cancer-related acute ischemic stroke (AIS) that could potentially lead to earlier diagnosis of cancer in these patients.

Cancer is commonly diagnosed in patients with AIS. Since blood mRNA profiles can distinguish AIS mechanisms, a team of cancer investigators from several institutions including Weill Cornell Medical College (New York, NY, USA) and the University of California, Davis (USA) hypothesized that cancer-related AIS would have a distinctive gene expression profile.


To test this theory, the investigators evaluated four groups of 10 subjects prospectively enrolled at three centers from 2009 to 2018. This population included the group of interest with active solid tumor cancer and AIS and three control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke, and total RNA was analyzed using 3′ mRNA sequencing.

Results revealed that more than half of strokes in the cancer-stroke group were not caused by traditional risk factors. In total, more than 12,000 genes were analyzed and comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were found to be differentially expressed. These genes were linked to upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including interleukin-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1).

"We clearly see that cancer-stroke patients have a unique gene expression profile," said first author Dr Babak Navi, chief of stroke and hospital neurology at Weill Cornell Medical College. "No one before had differentiated gene expression between patients with cancer, stroke, or both. A blood test would be easier, safer, and less expensive than a CT or PET scan to diagnose cancer."

The report was published in the September 12, 2019, online edition of the journal Stroke.

Related Links:
Weill Cornell Medical College
University of California, Davis