Intact and cleaved plasma soluble urokinase receptor in XXXX with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab.

@entity1 @entity984 @entity10431 @entity470
Circulating forms of the @entity10431 ( @entity10431 ) are associated with prognosis in @entity1 with colorectal cancer. Preclinical studies have shown that @entity10431 can influence the state of phosphorylation and signalling activity of the @entity470 ( @entity470 ) in a ligand-independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved @entity10431 (I-III)+(II-III) levels could identify a subpopulation of @entity1 with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were available from 453 @entity1 treated in the NORDIC VII study. @entity1 were randomized between FLOX and FLOX   +   cetuximab. The levels of @entity10431 (I-III)+(II-III) were determined by time-resolved fluorescence immunoassay. We demonstrated that higher baseline plasma @entity10431 (I-III)+(II-III) levels were significantly associated with shorter progression-free survival (PFS) (HR   =   1.30, 1.14-1.48, p   =   0.0001) and overall survival (OS) (HR   =   1.75, 1.52-2.02, p   <   0.0001). Multivariate Cox analysis showed that plasma @entity10431 (I-III)+(II-III) was an independent biomarker of short OS (HR   =   1.45, 1.20-1.75, p   =   0.0001). There were no significant interactions between plasma @entity10431 (I-III)+(II-III) levels, @entity984 mutational status and treatment either PFS (p   =   0.43) or OS (p   =   0.095). However, further explorative analyses indicated that @entity1 with low levels of circulating suPAR and a @entity984 wild-type tumor have improved effect from treatment with FLOX   +   cetuximab as compared to @entity1 with @entity984 wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set.
