IL-8 and thrombospondin-1 as prognostic markers in patients with metastatic colorectal cancer receiving bevacizumab

Giorgia Marisi,1 Emanuela Scarpi,2 Alessandro Passardi,3 Oriana Nanni,2 Flavia Pagan,2 Martina Valgiusti,3 Andrea Casadei Gardini,3 Luca Maria Neri,4 Giovanni Luca Frassineti,3 Dino Amadori,3 Paola Ulivi1 1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; 2Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; 3Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; 4Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44100, Italy Purpose: Bevacizumab (B) plus chemotherapy (CT) is a common choice for first-line treatment of metastatic colorectal cancer. Molecular predictors of B efficacy have still not been identified. We analyzed the role of 22 angiogenesis-associated proteins in patient outcome.Patients and methods: Serum samples collected at baseline and at the first clinical evaluation were available for 58 patients enrolled in the randomized multicenter ITACa trial and who received CT+ B. Serum protein levels were determined using multiplex ELISA.Results: Patients with baseline ≥145 pg/mL IL-8 showed shorter median progression-free survival and overall survival (OS) than those with lower levels (6.5 vs 6. 12.6 months; HR 7.39, P<0.0001 and 8.7 vs 28.8 months, HR 7.68, P<0.001, respectively). Moreover, patients with baseline thrombospondin-1 levels ≥12,000 ng/mL had a better median OS than those with lower levels (34.5 vs 13.1 months, HR 0.43, P=0.007). Patients with a ≥20% reduction in IL-8 levels from baseline to first clinical evaluation showed a better progression-free survival and OS than the others (HR 0.41, P=0.005 and HR 0.43, P=0.007, respectively).Conclusion: Baseline IL-8 and thrombospondin-1 levels and reduced IL-8 during B treatment could represent potential prognostic markers in metastatic colorectal cancer. Keywords: serum biomarkers, targeted therapy, IL-8, angiogenesis, chemotherap