Prognostic value of plasma levels of HIF-1β and PGC-1β in breast cancer

Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1 beta (HIF-1 beta) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator-activated receptor eta coactivators 1 beta (PGC-1 beta) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1 beta and PGC-1 beta can be implemented as predictive biomarker in breast cancer. HIF-1 beta and PGC-1 beta plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1 beta and PGC-1 beta levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1 beta and PGC-1 beta were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1 beta showed independent prognostic value. Our data suggests that HIF-1 beta and PGC-1 beta may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.