First indication of possible role of blood coagulation in lung carcinogenesis

13 Aug 2019 | Source: German Cancer Research Centre (DKFZ)

Thrombophilia promotes the progression and metastasis of lung cancer. Up to now, it was not known whether coagulation is also conducive to tumorigenesis. For the first time, researchers from the German Cancer Research Center have now identified a possible role of blood coagulation in the development of lung cancer.

In the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), the scientists examined whether prediagnostic coagulation markers can be used to predict the risk of lung cancer. To do so, they determined the level of various factors involved in coagulation, including fibrinogen, soluble glycoproteins, and soluble P-selectin.

These characteristic coagulation proteins were determined in initial blood samples of 2,480 EPIC participants. The coagulation factor concentrations of 190 EPIC study subjects who developed lung cancer in the course of the follow-up period of the EPIC study were then compared with these initial values.

"Our work showed a significant association between higher blood concentrations of both fibrinogen and soluble P-selectin long before manifestation of the disease and a higher risk of lung cancer," lead author Mirja Grafetstätter explained, summarizing the main finding of the study. "This is the first indication that increased coagulation activity not only promotes existing lung cancer, but may also be involved in carcinogenesis. A causal relationship still needs to be verified in further studies, however."

"This is the first time that a prospective study has supported the hypothesis that thrombophilia may promote the genesis of lung cancer," remarked principal investigator Tilman Kühn. The clearest relationship between cancer risk and blood coagulation was demonstrated for two blood coagulation cascade proteins, fibrinogen and soluble P-selectin. However, whether the concentrations of the two proteins can be used in future as a prediagnostic marker of individual lung cancer risk cannot be established until the current results have been verified by independent studies.

Fibrinogen is a coagulation factor that triggers activation of the blood platelets and their subsequent clotting. P-selectin is an important surface molecule expressed by endothelial cells and activated blood platelets; it mediates interaction between platelets and tumor cells and plays a particular role in metastasis, among other things.

The work was supported by third-party funding from the World Cancer Research Fund and the German Center for Lung Research (DZL).

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. At DKFZ, more than 1,300 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. DKFZ’s Cancer Information Service (KID) provides individual answers to all questions about cancer for patients, the general public, and health care professionals. Jointly with partners from Heidelberg University Hospital, DKFZ runs the National Center for Tumor Diseases (NCT) located in Heidelberg and Dresden, and, also in Heidelberg, the Hopp Children’s Cancer Center (KiTZ). In the German Cancer Consortium (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center at the NCT and DKTK sites is an important contribution to the endeavor of translating promising approaches from cancer research into the clinic in order to improve the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.