Platelet CKB expression is associated with elevated serum CK-BB and metastatic phenotype in lung cancer

The abnormal increase of serum creatine kinase-MB activity exceeding total creatine kinase activity is an uncommon and paradoxical laboratory finding often observed in patients with cancer. However, the underlying origin and clinical relevance of this phenomenon remain unclear. In this study, we analyzed a large cohort of cancer patients presenting with this biochemical abnormality. We first characterized the cancer types and stages most frequently associated with this pattern, finding enrichment in colorectal and lung cancers, particularly at advanced stages. Serum isoenzyme electrophoresis revealed that the abnormal elevation was not due to myocardial damage but instead driven by high levels of brain-type and mitochondrial creatine kinase isoforms. We introduced a new composite index integrating these non-cardiac isoenzymes, which was correlated with poor prognosis, especially in colorectal cancer. Notably, we identified an unexpected elevation of creatine kinase brain-type messenger RNA in platelets from lung cancer patients. This expression level was significantly higher than that found in serum and showed a strong positive correlation, suggesting that platelets may contribute to the circulating isoenzyme pool. This observation was supported by analysis of a public dataset of tumor-educated platelets, which confirmed higher creatine kinase expression in lung cancer patients. Additional single-cell sequencing data showed that distant metastatic lesions, but not primary tumors, exhibited elevated creatine kinase expression. Functional gene enrichment analysis revealed associated pathways involved in metabolism, oxidative stress, and intercellular signaling. These findings suggest that platelet-related creatine kinase may be linked to metastatic potential in lung cancer and represent a previously underrecognized component in cancer-associated biochemical alterations.