Colorectal cancer (CRC) is one of the most frequent human neoplasia and, in spite treatment improvements, the related mortality remains high and the lack of clinical prognostic biomarkers remains. Knowing that proinflammatory cytokines are potential targets for anticancer therapy, we developed an experimental approach based on the use of cytokine data-driven computational models of the immune response to apply to a group of 37 CRC patients. The relationship between cytokines, KIR and FcgRIIIa 158G/T (F/V) polymorphism was evaluated. Serum cytokines, receptors, redox system molecules (IL-6, sIL6R, IFN-gamma, IL-4, IL-10, IL-2, sIL-2R, TGF-beta, sCD30, Thioredoxin1 and Trx1 reductasi), KIR and FcgRIIIa gene polymorphisms were used as molecular targets. Preliminary results from multivariate statistical analysis (Statgraphics software systems) suggested that in our patients a specific pathway of clinical biomarkers, responsible of establishment and progression of cancer, exists and that the increase of TGF-beta, IL6, IL-4 and decrease of IL2 cytokine levels were related to KIR and CD16 molecules. TGFbeta, that leads to a decreased ability of NK cells to kill target cells, was negatively correlated with activating KIR2DS1 (p=0.04 r-0.35) and KIR3DS1(p=0.04 r-0.48) and with the inhibitory KIR2DL5A (p=0.04 r-0.35). IL6, that aids tumor growth and is a malignant index, is correlated to activating KIR2DS3 (p=0.049 r-0.33) and IL2 is positively associated with KIR2DL5B (p=0.047 r0.33) and KIR2DS3 (p=0.049 r0.33) and negatively with KIR3DL1 (p=0.036 r-0.35). Exploring the association between FcgRIIIa 158G/T and KIRs we detected a significant association between FcgRIIIa -158 T/T genotype and both KIR2DL3 and KIR2DS2 (p=0.019 r- 0.40; and p=0.05 r 0.33 respectively). Although preliminary data encourage the use of this panel of prognostic clinical biomarkers for the definition of personalised cancer treatments, more basic studies are required to confirm its utility in patients.
IDENTIFICATION OF BIOMARKERS FOR TAILORED TREATMENT OF COLORECTAL CANCER: RELATIONSHIP BETWEEN CYTOKINES, KIR AND CD16A GENE POLYMORPHISMS
Aureli Anna;Pellegrini Patrizia;Del Beato Tiziana;Canossi Angelica
2016
Abstract
Colorectal cancer (CRC) is one of the most frequent human neoplasia and, in spite treatment improvements, the related mortality remains high and the lack of clinical prognostic biomarkers remains. Knowing that proinflammatory cytokines are potential targets for anticancer therapy, we developed an experimental approach based on the use of cytokine data-driven computational models of the immune response to apply to a group of 37 CRC patients. The relationship between cytokines, KIR and FcgRIIIa 158G/T (F/V) polymorphism was evaluated. Serum cytokines, receptors, redox system molecules (IL-6, sIL6R, IFN-gamma, IL-4, IL-10, IL-2, sIL-2R, TGF-beta, sCD30, Thioredoxin1 and Trx1 reductasi), KIR and FcgRIIIa gene polymorphisms were used as molecular targets. Preliminary results from multivariate statistical analysis (Statgraphics software systems) suggested that in our patients a specific pathway of clinical biomarkers, responsible of establishment and progression of cancer, exists and that the increase of TGF-beta, IL6, IL-4 and decrease of IL2 cytokine levels were related to KIR and CD16 molecules. TGFbeta, that leads to a decreased ability of NK cells to kill target cells, was negatively correlated with activating KIR2DS1 (p=0.04 r-0.35) and KIR3DS1(p=0.04 r-0.48) and with the inhibitory KIR2DL5A (p=0.04 r-0.35). IL6, that aids tumor growth and is a malignant index, is correlated to activating KIR2DS3 (p=0.049 r-0.33) and IL2 is positively associated with KIR2DL5B (p=0.047 r0.33) and KIR2DS3 (p=0.049 r0.33) and negatively with KIR3DL1 (p=0.036 r-0.35). Exploring the association between FcgRIIIa 158G/T and KIRs we detected a significant association between FcgRIIIa -158 T/T genotype and both KIR2DL3 and KIR2DS2 (p=0.019 r- 0.40; and p=0.05 r 0.33 respectively). Although preliminary data encourage the use of this panel of prognostic clinical biomarkers for the definition of personalised cancer treatments, more basic studies are required to confirm its utility in patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
