RNA blood levels of osteopontin splice variants are cancer markers

PURPOSE Despite a sizeable and continuously growing literature on osteopontin and cancer the molecule has not yet found entry into clinical diagnostics. Our identification of spliced variants that are more specific for cancer than the full-length transcript has opened new possibilities for reaching this goal. METHODS Here we have developed a real-time RT-PCR blood test and evaluated it in a pilot study of breast, lung, pancreatic, gynecologic, and other cancers, compared to non-cancer controls. RESULTS Osteopontin-b was increased in lung cancers and pancreatic cancers. When applying a cutoff of 2 standard deviations above normal, elevation in osteopontin-b transcripts detected over 40% of lung cancers. Osteopontin-c was increased in gynecologic and pancreatic cancers. Elevation in osteopontin-c of 2 standard deviations above the normal mean value also detected a fraction of breast cancers and lung cancers, suggesting heterogeneity within those types of tumors. Specifically, breast carcinomas were associated with significantly higher levels of osteopontin-c mRNA in the blood than carcinomas in situ. In lung cancer patients, the osteopontin-c blood RNA levels had an increasing trend with tumor grade. CONCLUSIONS Osteopontin-b and -c in the blood are biomarkers for distinct cancers. Our investigations may have bearing on cancer screening and diagnosis.