Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor.

OBJECTIVES

Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC).

METHODS

Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were referred to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up.

RESULTS

Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor.

CONCLUSIONS

Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.