Overall, we confirmed that expression of KAI1 mRNA decreased from normal tissue, through localised cancer to bony metastases (P=0.055, tending to significance), while levels of p53 staining significantly increased with cancer progression (P=0.046).
Mechanistically, these effects are likely mediated through suppression of multiple signaling pathways, upregulation of p53 and downregulation of oncogenes leading to anti-proliferative effects and reduced metastases to bone, a phenotype associated with poor clinical outcome.
MET alterations were observed in 31 patients (7.1%) and correlated with bone metastasis (P = 0.007), with TP53 (P = 0.001) and PTEN (P = 0.003) abnormalities, and with an increased number of alterations (median, 4 vs 1, P = 0.001) (all multivariable analyses).
Our results also provided possible molecular mechanisms in which the ribosome and p53 pathways may respectively contribute to bone metastasis and local recurrence of metastasis.