Platelet CKB as a potential contributor to serum creatine kinase abnormalities and metastasis in cancer patients.

An unusual clinical laboratory phenomenon-serum creatine kinase-MB (CK-MB) activity exceeding total creatine kinase (CK) activity (CK-MB > CK)-is frequently observed in cancer patients, yet its molecular origin and relevance to tumor biology remain unclear. We conducted an integrated analysis combining a large retrospective cancer cohort (n = 1,651), serum CK isoenzyme electrophoresis, and qRT-PCR analysis of paired serum and platelet samples. Public RNA-sequencing datasets, including tumor-educated platelets (TEPs) and single-cell data from lung cancer metastases, were utilized to explore the molecular basis and clinical significance of CK isoenzyme alterations. Colorectal and lung cancers were the most frequently associated malignancies with CK-MB > CK abnormalities, particularly in advanced stages. Electrophoresis and transcript profiling revealed that this paradoxical elevation was driven by aberrant increases in non-cardiac CK isoenzymes, especially brain-type creatine kinase (CK-BB) and mitochondrial CK. A composite index (CK-Sub), integrating CK-BB and mitochondrial CK isoforms, was developed and found to be potentially associated with tumor progression. Notably, CKB mRNA was significantly elevated in platelets from lung cancer patients and exceeded paired serum levels, with a strong positive correlation (R