Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 7;21(1):364.
doi: 10.1186/s12885-021-08091-1.

Significance of coagulation and fibrinolysis markers for benign and malignant soft tissue tumors

Kunihiro Asanuma  1 , Tomoki Nakamura  2 , Tomohito Hagi  2 , Takayuki Okamoto  3 , Kouji Kita  2 , Koichi Nakamura  2 , Yumi Matsuyama  2 , Keisuke Yoshida  2 , Yumiko Asanuma  2 , Akihiro Sudo  2
Affiliations

Significance of coagulation and fibrinolysis markers for benign and malignant soft tissue tumors

Kunihiro Asanuma et al. BMC Cancer. .

Abstract

Background: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS.

Methods: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters.

Results: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p = 0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden's index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively. The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p = 0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p = 0.0404) .

Conclusions: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.

Keywords: And thrombin-antithrombin III complex; Coagulation; D-dimer; Fibrinolysis; Metastasis; Plasmin-α2 plasmin inhibitor complex; Prognosis; Soft tissue sarcoma; Soluble fibrin.

PubMed Disclaimer

Conflict of interest statement

All authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Evaluation of DD, PIC, SF and TAT in patients with benign tumors or STS. DD, PIC, and SF levels were significantly higher in STS (S) than in benign (B) tumors (Mann-Whitney test)
Fig. 2
Fig. 2
ROC analysis. Thresholds values were determined by based on the Youden’s index. Thresholds for DD, PIC, SF and TAT were 0.37, 0.80, 0.90 and 0.82, respectively. Youden’s index values are presented as threshold (specificity, sensitivity)
See this image and copyright information in PMC

References

    1. Lundbech M, Krag AE, Christensen TD, Hvas AM. Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients. Thromb Res. 2020;186:80–85. doi: 10.1016/j.thromres.2019.12.018. - DOI - PubMed
    1. Soe G, Kohno I, Inuzuka K, Itoh Y, Matsuda M. A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives: its application to the measurement of soluble fibrin in plasma. 1996. - PubMed
    1. Kwaan HC. The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev. 1992;11(3–4):291–311. doi: 10.1007/BF01307184. - DOI - PubMed
    1. Kılıc M, Yoldas O, Keskek M, Ertan T, Tez M, Gocmen E, Koc M. Prognostic value of plasma D-dimer levels in patients with colorectal cancer. Color Dis. 2008;10(3):238–241. doi: 10.1111/j.1463-1318.2007.01374.x. - DOI - PubMed
    1. Xu L, He F, Wang H, Gao B, Wu H, Zhao S. A high plasma D-dimer level predicts poor prognosis in gynecological tumors in East Asia area: a systematic review and meta-analysis. Oncotarget. 2017;8(31):51551–51558. doi: 10.18632/oncotarget.17936. - DOI - PMC - PubMed

LinkOut - more resources