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Article type: Research Article
Authors: Asanuma, Kunihiroa; * | Nakamura, Tomokia | Asanuma, Yumikoa | Kakimoto, Takuyaa | Yada, Yukia | Hagi, Tomohitoa | Kita, Koujia | Matsumine, Akihikob | Sudo, Akihiroa
Affiliations: [a] Department of Orthopedic Surgery, Mie University School of Medicine, Tsu, Mie, Japan | [b] Departments of Orthopedic Surgery, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, Japan
Correspondence: [*] Corresponding author: Kunihiro Asanuma, 514-8507 Mie University, Orthopedic Surgery, 2-174, Edobashi, Tsu, Mie, Japan. Tel.: +81 59 231 5022; Fax: +81 59 231 5211; E-mail: kasanum@gmail.com.
Abstract: BACKGROUND:Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin. OBJECTIVES: To clarify the correlation between serum TM levels and clinicopathological parameters. METHODS: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival. RESULTS: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p= 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p= 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1–3 (p= 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p= 0.0147; OS: HR 3.60, p= 0.0557) in grades 1–3. CONCLUSIONS: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy.
Keywords: Thrombomodulin, soft tissue tumor, soft tissue sarcoma, metastasis, prognosis
DOI: 10.3233/CBM-182075
Journal: Cancer Biomarkers, vol. 26, no. 2, pp. 163-170, 2019
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