Title |
Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF
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Published in |
Breast Cancer Research, March 2015
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DOI | 10.1186/s13058-015-0548-5 |
Pubmed ID | |
Authors |
Mari Tinholt, Hans Kristian Moen Vollan, Kristine Kleivi Sahlberg, Sandra Jernström, Fatemeh Kaveh, Ole Christian Lingjærde, Rolf Kåresen, Torill Sauer, Vessela Kristensen, Anne-Lise Børresen-Dale, Per Morten Sandset, Nina Iversen |
Abstract |
Hypercoagulability in malignancy is known to increase the risk of thrombosis, but is also involved in cancer progression. Experimental studies suggest that tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are involved in cancer biology as a tumor- promoter and suppressor, respectively, but the clinical significance is less clear. Here, we aimed to investigate the clinical relevance of TF and TFPI genetic and phenotypic diversity in breast cancer. The relationship between tumor messenger RNA (mRNA) expression and plasma levels of TF and TFPI (α and β), tagging single nucleotide polymorphisms (tagSNPs) in F3 (TF) (n = 6) and TFPI (n = 18), and clinicopathological characteristics and molecular tumor subtypes were explored in 152 treatment naive breast cancer patients. The effect of tumor expressed TF and TFPIα and TFPIβ on survival was investigated in a merged breast cancer dataset of 1881 patients. Progesterone receptor negative patients had higher mRNA expression of total TFPI (α + β) (P = 0.021) and TFPIβ (P = 0.014) in tumors. TF mRNA expression was decreased in grade 3 tumors (P = 0.003). In plasma, total TFPI levels were decreased in patients with larger tumors (P = 0.013). SNP haplotypes of TFPI, but not TF, were associated with specific clinicopathological characteristics like tumor size (odds ratio (OR) 3.14, P = 0.004), triple negativity (OR 2.4, P = 0.004), lymph node spread (OR 3.34, P = 0.006), and basal-like (OR 2.3, P = 0.011) and luminal B (OR 3.5, P = 0.005) molecular tumor subtypes. Increased expression levels of TFPIα and TFPIβ in breast tumors were associated with better outcome in all tumor subtypes combined (P = 0.007 and P = 0.005) and in multiple subgroups, including lymph node positive subjects (P = 0.006 and P = 0.034). This study indicates that genetic and phenotypic variation of both TFPIα and TFPIβ, more than TF, are markers of cancer progression. Together with the previously demonstrated tumor suppressor effects of TFPI, the beneficial effect of tumor expressed TFPI on survival, renders TFPI as a potential anticancer agent, and the clinical significance of TFPI in cancer deserves further investigation. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 4 | 20% |
Student > Master | 3 | 15% |
Student > Doctoral Student | 2 | 10% |
Researcher | 2 | 10% |
Student > Ph. D. Student | 2 | 10% |
Other | 3 | 15% |
Unknown | 4 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 9 | 45% |
Biochemistry, Genetics and Molecular Biology | 3 | 15% |
Unspecified | 1 | 5% |
Immunology and Microbiology | 1 | 5% |
Engineering | 1 | 5% |
Other | 0 | 0% |
Unknown | 5 | 25% |