Soluble CD40 ligand plasma levels in lung cancer.
OBJECTIVE
Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation.


METHODS
Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples.


RESULTS
Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L.


CONCLUSIONS
These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.
Roselli
Mario
M
Medical Oncology, Department of Surgery, University Tor Vergata, Rome, Italy.
Mineo
Tommaso C
TC
Basili
Stefania
S
Martini
Francesca
F
Mariotti
Sabrina
S
Aloe
Simona
S
Del Monte
Girolamo
G
Ambrogi
Vincenzo
V
Spila
Antonella
A
Palmirotta
Raffaele
R
D'Alessandro
Roberta
R
Davì
Giovanni
G
Guadagni
Fiorella
F
Ferroni
Patrizia
P
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023201:CD40 Ligand / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007118:Immunoassay; D008175:Lung Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D011516:Prothrombin / Q000737:chemistry; D013917:Thrombin / Q000378:metabolism
D016207:Cytokines; D019007:P-Selectin; D023201:CD40 Ligand; D011516:Prothrombin; D013917:Thrombin