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Expression of the MET oncogene correlates with upregulation of coagulation factor XII and procoagulant disorders in colorectal cancer

ABSTRACT: Cancer patients often develop hemostasis disorders whose pathogenesis is poorly understood. Previous work in mouse models has shown that these disorders can be sustained by the MET oncogene by transcriptional upregulation of hemostasis genes. Here we investigated the correlation between the procoagulant state of colorectal cancer patients, and overexpression of MET and hemostasis genes in the tumor. We found that, in a patient subset, blood levels of D-dimer and coagulation factor XII (F12) were frequently elevated, and reverted towards normality after surgery. Global expression profiling of tumor tissues and adjacent mucosae revealed a significant correlation between high D-dimer levels in the blood, and overexpression of MET in the tumor. An “hemostasis gene signature”, including F12, cyclo-oxygenase 2, thromboxane synthase-1, plasminogen activator inhibitor-1, urokinase-type plasminogen activator and protein C receptor was associated with MET overexpression. This association was confirmed in an independent 173-sample CRC dataset. The mechanistic link between MET signaling and F12 expression was established experimentally in cell lines. These data indicate that MET contributes to the pathogenesis of coagulation disorders in CRC by upregulation of hemostasis genes including F12, and provide a candidate biomarker for the CRC-associated procoagulant state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52060 | GEO | 2022/12/30

REPOSITORIES: GEO

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Homo sapiens

Project description:Expression of the MET oncogene correlates with upregulation of coagulation factor XII and procoagulant disorders in colorectal cancer

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