NOVEL MARKERS OF BONE METASTATIC PROCESS - USE OF MULTIPLEX ASSAY: A PILOT STUDY

The rapidly developing multiplex analytical technology opens the doors for multimarker blood monitoring of cancer processes, which can further help in bone metastasis detection. One of these tools can be the multiplex Human Bone Panel introduced in 2007. The aim of this study is to monitor the usefulness of multiplex bone metabolism panel for tumour induced bone disease (bone metastases) detection by serum test and to set up the normal serum levels for parameters included in multiplex panel. Methods: The following patient cohorts were studied: Group 0: control group - 20 healthy blood donors - (8 men, 12 women); Group 1: 13 cancer patients with bone metastases; Group 2: 11 cancer patients without bone metastases. Serum levels of osteoprotegerin, osteopontin, osteocalcin, parathormon and leptin were measured by multiplex xMAP technology with the use of Human Bone Panel A. Routinely used serum bone markers: PINP, PIIINP, ostase, ICTP and 25-hydroxyvitamin D were assessed for groups 1 and 2. Blood marker levels were compared between groups by Wilcoxon test. Normal values for multiplex markers were set as a 95 percentile of group 0. A scoring system was created for better discrimination of group 1 and group 2 - each value above normal level is scored by 1 point, points for osteoprotegerin, osteopontin, P3NP, ICTP and ostase were counted up. Results: Significantly higher levels of osteoprotegerin and osteopontin in both cancer groups compared to the control group were found. Significantly higher levels of PIIINP and ostase were found in group 1 compared to group 2. Three of 4 patients with multiple bone metastases had values above the set normal values both for osteoprotegerin and osteopontin in comparison to all other cancer patients, where only one of these markers was positive. A positive score of 3 or higher was counted for 46% of patients in group 1 (6/13) in comparison to 9% in group 2 (1/11), and score 2 or higher for 61.5% patients (8/13) in group 1 in comparison to 36% (4/11) in group 2. Conclusion: It has been shown that multiplex immunoanalysis can be used for oncology, however the most promising have turned out to be osteoprotegerin and osteopontin, which agree with literature sources. It seems that the incorporation of other bone markers such as PIIINP or ostase into the multiplex panel would be very useful for oncology, nevertheless, an investigation on a larger cohort is necessary.