Oncotarget

Research Papers:

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

Feng-Feng Cai _, Cheng Xu, Xin Pan, Lu Cai, Xiao-Yan Lin, Su Chen and Ewelina Biskup

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Oncotarget. 2016; 7:77793-77806. https://doi.org/10.18632/oncotarget.12796

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Abstract

Feng-Feng Cai1,*, Cheng Xu1,*, Xin Pan2, Lu Cai1, Xiao-Yan Lin1, Su Chen3, Ewelina Biskup4

1Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China

2Department of Central Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China

3Department of Molecular and Cellular Biology, School of Forensic Sciences, Xi’an Jiao Tong University Health Science Center, Xi’an, Shaanxi, PR China

4Department of Oncology, Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland

*These authors have contributed equally to this work

Correspondence to:

Feng-Feng Cai, email: [email protected]

Su Chen, email: [email protected]

Ewelina Biskup, email: [email protected]

Keywords: breast cancer, HIF-1α, PGC-1α, prognosis, ELISA

Received: July 22, 2016     Accepted: October 10, 2016     Published: October 21, 2016

ABSTRACT

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


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