Plasma Fibrinogen and sP-Selectin are associated with the risk of lung cancer in a prospective study
Menée à partir d'échantillons sanguins prélevés sur 2 480 témoins et 190 personnes atteintes d'un cancer du poumon, cette étude analyse l'association entre les niveaux plasmatiques des biomarqueurs de l'activation plaquettaire et de la coagulation (sP-sélectine et fibrinogène) et le risque de développer la maladie
Background : While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether pre-diagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case-cohort design. Methods : Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n=2,480) and incident cases of lung cancer (n=190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain Hazard Ratios (HRs) of lung cancer across quartiles of biomarker levels. Results : Fibrinogen (HR highest vs. lowest quartile: 1.91 [95 % confidence interval: 1.09, 3.34]) and sP-Selectin (HR: 2.51 [1.39, 4.52]) were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814. Conclusions : Our findings indicate that enhanced platelet activation and a pro-coagulative state contribute to lung carcinogenesis. Impact : The present prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.