Longitudinal Dynamics of Coagulation and Angiogenesis Markers in Cancer Patients During and After Chemotherapy

Abstract

Hemostatic parameters have been investigated as molecular determinants of tumor progression. To analyze the dynamics of microparticle-associated tissue factor activity (MPTF), tissue factor antigen (TF-Ag), and angiopоietin-2 (ANG-2) in cancer patients before, during, and after active treatment and to explore their potential as biomarkers for metastatic occurrence and death. Blood for the analysis of MPTF, TF-Ag, ANG-2, and conventional hemostatic tests was sampled in 111 patients with various cancers at 4 consecutive visits: before first chemotherapy cycle, after 3 courses, at the sixth course, and 3 months after chemotherapy cessation. Patients were followed up until metastatic progression/death or the end of the study. MPTF did not change during chemotherapy, but increased significantly after treatment cessation. Total TF-Ag and ANG-2 decreased throughout active treatment. Significant drop of their levels was observed 3 months post therapy cessation. Progressive disease was significantly associated with higher pre-chemotherapy TF-Ag and fibrinogen. Elevated baseline levels of fibrinogen were associated with increased risk of shortened progression free survival. Cessation of chemotherapy is associated with significant change of hemostatic parameters. Pre-chemotherapy levels of TF-Ag and fibrinogen may be informative of disease state and prognosis.

The effects of coagulation factors and their inhibitors on proliferation and migration in colorectal cancer

“…Exogenous TF had no effect on proliferation at the 50–500 pg/mL concentration range, which was chosen to reflect reported colorectal cancer patient plasma levels 27 . We did not increase the concentration of TF administered beyond this (Figure 1E,F).…”

“…The absence of a pro‐proliferative response in both SW620 and DLD‐1 cells treated with tissue factor could indicate that the experiment concentrations based on colorectal cancer patient plasma levels (50–500 pg/mL 27 ) were too low. We based the tissue factor concentrations on plasma levels as the marked increase in tissue factor expression in colorectal tumour epithelium and stroma compared to surrounding normal cells makes it very difficult to accurately quantify concentrations in tissue 32 .…”

Fibrinogen and tumors

“…2 The role and mechanism of Fg in tumors 2.1 Plasma Fg levels in tumor patient cohorts Elevated plasma fibrinogen(Fg) levels consistently manifest in diverse tumor patient cohorts (9). In lung, rectal, and stomach cancers, heightened Fg levels correlate with poorer survival (10)(11)(12) are recognized as an independent prognostic marker (4).…”