Colorectal cancer (CRC) is the third most common type of cancer worldwide and the discovery and validation of new biomarkers is a continuing challenge of the scientists in this field. It is known that oxidative state and inflammatory cytokines are regulators of tumour-associated inflammation and tumorigenesis, and the genetic distribution of killer immunoglobulin-like receptors (KIRs) and different binding affinity of the Fc? receptor IIIA (CD16A), Fcy receptor IIa (CD32A) may affect the CRC pathogenesis. Our previous data show that the systems of Thioredoxin 1 (Trx1, a redox molecule) and the CD30 (Trx1 receptor on immune cells, including NK and dendritic cells) represent a double target/biomarker and testing the effect of this system with cytokines, KIRs, CD16A and CD32A genotypes on the susceptibility to develop CRC has represented our goal. So, we hypothesized that serum levels of cytokines, sCD30 and Trx1/RTrx1 combined with KIR, CD16A and CD32A genic polymorphisms could be clinical indicators in CRC. To do this, we evaluated, through biological system studies, serum levels of sCD30, Trx1/RTrx1 and cytokines (ELISA test) and KIR and CD16 and CD32A polymorphisms (SSP and SBT genotyping) in 146 CRC patients and 219 healthy subjects. Statistical analysis was done using a multivariate approach. Our results were as follows: a) CRC progression is associated to an increase of sera levels of IL6 (p=0.0001), IL10 (p=0.00001) and TGFbeta (p=0.0007) and a decrease of IL2 level (p=0.0003); b) Trx1/RTrx1 and sCD30 are positively associated to CRC progression (p=0.003 and 0.001 respectively); c) the presence of >2 aKIR, FcyRIIa-131H/H and FcyRIIIa-158V/V seems protective of disease and index of therapeutic benefit, while the presence of <3 aKIR genes and of FcyRIIa-131R/R and FcyRIIIa-158F/F genotypes increases susceptibility to CRC. In conclusion, we propose a new model of prognostic biomarkers that could be suitable as risk indicator of CRC and for a personalized clinic/therapeutic approach.
COLORECTAL CANCER: NEW BIOMARKERS SYSTEM IN PREVENTION AND TREATMENT
Patrizia Pellegrini;Angelica Canossi;Anna Aureli;Tiziana Del Beato;
2017
Abstract
Colorectal cancer (CRC) is the third most common type of cancer worldwide and the discovery and validation of new biomarkers is a continuing challenge of the scientists in this field. It is known that oxidative state and inflammatory cytokines are regulators of tumour-associated inflammation and tumorigenesis, and the genetic distribution of killer immunoglobulin-like receptors (KIRs) and different binding affinity of the Fc? receptor IIIA (CD16A), Fcy receptor IIa (CD32A) may affect the CRC pathogenesis. Our previous data show that the systems of Thioredoxin 1 (Trx1, a redox molecule) and the CD30 (Trx1 receptor on immune cells, including NK and dendritic cells) represent a double target/biomarker and testing the effect of this system with cytokines, KIRs, CD16A and CD32A genotypes on the susceptibility to develop CRC has represented our goal. So, we hypothesized that serum levels of cytokines, sCD30 and Trx1/RTrx1 combined with KIR, CD16A and CD32A genic polymorphisms could be clinical indicators in CRC. To do this, we evaluated, through biological system studies, serum levels of sCD30, Trx1/RTrx1 and cytokines (ELISA test) and KIR and CD16 and CD32A polymorphisms (SSP and SBT genotyping) in 146 CRC patients and 219 healthy subjects. Statistical analysis was done using a multivariate approach. Our results were as follows: a) CRC progression is associated to an increase of sera levels of IL6 (p=0.0001), IL10 (p=0.00001) and TGFbeta (p=0.0007) and a decrease of IL2 level (p=0.0003); b) Trx1/RTrx1 and sCD30 are positively associated to CRC progression (p=0.003 and 0.001 respectively); c) the presence of >2 aKIR, FcyRIIa-131H/H and FcyRIIIa-158V/V seems protective of disease and index of therapeutic benefit, while the presence of <3 aKIR genes and of FcyRIIa-131R/R and FcyRIIIa-158F/F genotypes increases susceptibility to CRC. In conclusion, we propose a new model of prognostic biomarkers that could be suitable as risk indicator of CRC and for a personalized clinic/therapeutic approach.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
