Clinical implications of serum GDF15 propeptide as a biomarker for bone metastasis across common solid tumors: a real-world multi-institutional study.

Bone metastasis (BM) frequently occurs in various types of cancer, particularly in prostate (PCa), breast (BCa), renal (RCC), and lung cancers (LCa), yet no reliable biomarker has been established. In this study, we evaluated the clinical utility of serum growth differentiation factor 15 propeptide (sGDPP), secreted by both osteoblasts and osteoclasts, as a diagnostic biomarker for BM across common solid tumors. A total of 799 participants were enrolled, including 107 healthy donors, 242 patients with PCa, 113 patients with BCa, 159 patients with RCC, and 178 patients with LCa. Among the cancer patients, 398 had no BM and 294 had BM. The diagnostic performance for BM was compared among conventional biomarkers: alkaline phosphatase (ALP), lactate dehydrogenase (LDH), estimated glomerular filtration rate, osteocalcin, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b, procollagen type I N-terminal propeptide (PⅠNP), and sGDPP. Among all patients, ALP, LDH, PⅠNP, and sGDPP levels were significantly higher in patients with BM than in those without BM. Particularly, sGDPP showed the highest area under the curve values (0.91 in PCa, 0.80 in BCa, 0.81 in RCC, and 0.51 in LCa). Multivariate analysis showed sGDPP is an independent diagnostic biomarker for BM in PCa, BCa, and RCC (p < 0.01). Additionally, sGDPP in patients with osteoporosis did not significantly differ from that in healthy donors, suggesting that sGDPP increases only when tumor cells seed and proliferate in the bones. Overall, sGDPP demonstrated superior diagnostic performance compared to conventional biomarkers and may complement imaging tests in detecting BM.