肿瘤和原发性肉瘤骨转移患者TNFR1和血清素水平升高与生存状况差相关

Elevated TNFR1 and Serotonin in bone metastasis are correlated with poor survival following bone metastasis diagnosis for both carcinoma and sarcoma primary tumors.

Abstract
PURPOSE:
There is an urgent need for therapies that will reduce the mortality of patients with bone metastasis. In this study we profiled the protein signal pathway networks of the human bone metastasis microenvironment. The goal was to identify sets of interacting proteins that correlate with survival time following the first diagnosis of bone metastasis.

EXPERIMENTAL DESIGN:
Using Reverse Phase Protein Microarray technology we measured the expression of 88 end-points in the bone microenvironment of 159 bone metastasis tissue samples derived from patients with primary carcinomas and sarcomas.

RESULTS:
Metastases originating from different primary tumors showed similar levels of cell signaling across tissue types for the majority of proteins analyzed, suggesting that the bone microenvironment strongly influences the metastatic tumor signaling profiles. In a training set (72 samples), TNFR1, alone (p=0.0013) or combined with Serotonin (p=0.0004), TNFα (p=0.0214) and RANK (p=0.0226), was associated with poor survival, regardless of the primary tumor of origin. Results were confirmed by: a) analysis of an independent validation set (71 samples) and b) independent bioinformatic analysis using a support vector machine learning model. Spearman's rho analysis revealed a highly significant number of interactions intersecting with ERα S118, Serotonin, TNFα, RANKL and MMPs in the bone metastasis signaling network, regardless of the primary tumor. The interaction network pattern was significantly different in the short versus long survivors.

CONCLUSIONS:
TNFR1 and neuroendocrine-regulated protein signal pathways appear to play an important role in bone metastasis and may constitute a novel drug-targetable mechanism of seed-soil cross-talk in bone metastasis.

原文链接：http://www.ncbi.nlm.nih.gov/pubmed/23493346