Abstract
Using proteomic technology, we have discovered a novel protein in the serum of patients with bone metastases that is specific for cancer metastases in bone. To analyze this protein we used surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF) and a hybrid linear ion trap (Q TRAP) mass spectrometry system. Coupling of these types of instruments will enable amino aid sequencing and subsequent protein identification. A prospective study was undertaken in 47 patients with liver cancer, to identify which proteins were characteristic and predictive of bone metastasis. Of these patients, bone metastasis developed in 11 cases, and this protein was identified before bone metastasis was confirmed in bone scintigraphy of all patients. This result yielded a sensitivity of 100%. Also, among these patients, peak values of the protein were found in 10 cases. At present, the follow-up investigation is under way because the results of bone scintigraphy did not reveal bone metastasis. An important characteristic of the protein we identified was that it was detectable at about average at 6-11 months before diagnosis in these patients, much earlier than bone metastases can be imaged by bone scintigraphy. In addition, we quantified this protein from the areas under the curves by mass spectrometry, and found that the protein continued to increase in serum up to the time when bone metastasis was confirmed by bone scintigraphy and then decreased after the start of radiotherapy treatment.
