Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2019; 11(2): 117-138
Published online Feb 15, 2019. doi: 10.4251/wjgo.v11.i2.117
Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer
Anna Maria Berghella, Anna Aureli, Angelica Canossi, Tiziana Del Beato, Alessia Colanardi, Patrizia Pellegrini
Anna Maria Berghella, Anna Aureli, Angelica Canossi, Tiziana Del Beato, Alessia Colanardi, Patrizia Pellegrini, Istituto di Farmacologia Traslazionale, Consiglio Nazionale delle Ricerche, L’Aquila 67100, Italy
Author contributions: Berghella AM designed the research, performed the statistical study, analyzed and interpreted data and wrote and reviewed the manuscript; Pellegrini P performed the analyses of phenotypic antigens, the ELISA method for cytokine determination, the acquisition of statistical data, prepared the figures and tables and reviewed the manuscript; Aureli A performed FcγRIIa-131H/R and FcγRIIIa-158V/F polymorphism genotyping and reviewed the manuscript; Canossi A performed KIR polymorphism genotyping; Del Beato T performed polymorphism genotyping; Colanardi A collected biological material; All authors read and approved the final manuscript.
Institutional review board statement: All subjects in this study were enrolled in the L’Aquila, Pescara and Popoli Hospitals (Italy). Human studies were performed in accordance with the standards of the Ethics Committee (Good clinical practice, N°18-Prot. n 43/C.E) and all persons gave their written informed consent prior to their inclusion in the study.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Anna Maria Berghella, PhD, Research Scientist, Istituto di Farmacologia Traslazionale, Consiglio Nazionale delle Ricerche, Via G. Carducci 32, L’Aquila 67100, Italy. annamaria.berghella@cnr.it
Telephone: +39-862-318843
Received: September 19, 2018
Peer-review started: September 19, 2018
First decision: October 16, 2018
Revised: November 20, 2018
Accepted: January 10, 2019
Article in press: January 10, 2019
Published online: February 15, 2019
Processing time: 150 Days and 0.6 Hours
Abstract
BACKGROUND

Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer (CRC) onset that could improve clinical strategies.

AIM

To determine valid targets and a predictive biomarker’s system of chronicization of inflammation for cancer treatment.

METHODS

A group of 147 CRC patients was studied. Clinical diagnosis was confirmed histopathologically, and patients were sub-typed using the pathological tumor-node-metastasis classification. Thirteen colon adenoma patients and 219 healthy subjects were also studied. A system biology study on Thioredoxin1/CD30 redox-immune systems (Trx1/CD30), T helper cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131H/R and FcγRIIIa-158V/F was carried out. Enzyme-linked immunosorbent assay was performed to analyze sera. Genetic study was executed by polymerase chain reaction sequence-specific primers and sequence-based typing method. Statistical analysis was performed by using the “Statgraphics software systems”.

RESULTS

We found a positive increase between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there were distinct differences. Females showed a primary relationship between transforming growth factor beta (TGFβ) with Trx1, whereas males had one with TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between the Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor. This event happens through different gender-specific cytokine pathways. Our study demonstrated that the serum levels of Trx1/RTrx1, TGFβ/interleukin (IL)6 and TGFβ/IL4 combinations and the sCD30, IFNγ and IL2 combination constitute a predictive gender specific biomarker system. This is relevant for clinical screening to detect the risk of the potential development or progression of a tumor.

CONCLUSION

Oxidative stress on Trx1/CD30 is a trigger of cancer disease, and the selected oxidation and immune products are a biomarker system for aging and cancer.

Keywords: Aging and cancer biomarker; Cancer personalized treatments; Oxidation and immune biomarkers; Trx1/CD30 target; KIRs and FcγR polymorphisms; Th cytokines; Aging and disease; Cancer-related mechanisms

Core tip: Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer onset could improve clinical strategies. The aim was to establish if Trx1 and CD30 as dual targets, combined with cytokines and polymorphisms of killer immunoglobulin-like receptors, FcγRIIa-131H/R and FcγRIIIa-158V/F, was more effective. Serum measures of Trx1/CD30, RTrx1, multiple cytokine levels and polymorphisms of killer immunoglobulin-like receptors and FcγRIIa were used to estimate the effect of disease, age and gender to describe the variants in the biology of the redox immune system. Through these procedures, the redox immune fingerprint of health, aging and cancer states was determined.