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:
Corresponding author: Anna Maria Berghella, PhD, Research Scientist, Istituto di Farmacologia Traslazionale, Consiglio Nazionale delle Ricerche, Via G. Carducci 32, L’Aquila 67100, Italy.
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
Research background

The selection of prognostic biomarkers for the definition of personalized treatment in aging and colorectal cancer (CRC) onset and/or its progression is relevant to improve clinical strategies. Finding biomarkers able to identify the risk of developing degenerative processes linked to aging, which could lead to the onset of the disease, is a new challenge. Alterations in the physiological pathways involved in the regulation of redox and immunological systems have been identified in various types of tumors, such as CRC. The potential use of Trx1 and CD30 as targets and biomarkers for tumors has been widely described in literature, but results are still not relevant enough to improve the clinical strategies.

Research motivation

We have carried out this study to clarify if it was effective to use Trx and CD30 as dual target in combination with T helper cytokines and polymorphisms of KIRs, FcγRIIa-131H/R and FcγRIIIa-158V/F. The aim was to identify alterations in markers of redox-immune homeostasis that may be useful as a predictive biomarker system in health prediction and to identify personalized treatments to target age-related immune decline and cancer.

Research methods

The serum measures of Trx1/CD30, RTrx1, multiple cytokine levels and polymorphisms of KIR and FcγRIIa were used to estimate the effect of disease, age and gender interactions to describe the variants in the biology of the redox immune system. Using multivariate statistical procedures of correlation analysis and a matrix of correlation of all the redox immune and clinical parameters we have identified changes in the biology of the redox immune system relationships in both healthy aging and tumor disease progression. Through these procedures we determined the redox immune fingerprint of health, aging and cancer states.

Research results

We found positive increases between Trx1/RTrx1 levels and sCD30 level and increased age. With respect to the gender relationships, there are distinct differences: females show a primary relationship between TGFβ with Trx1 while males for TGFβ and RTrx1. Trx1/CD30 controls the redox immune homeostasis, and an imbalance in the relationship between Trx1/RTrx1 and sCD30 levels is linked to the onset and progression of tumor (but through different cytokine pathways in the male and female subjects). The study confirmed that the serum levels of Trx1/RTrx1, TGFβ/IL6 and TGFβ/IL4 combinations and the sCD30 IFNγ and IL2 combination are a predictive gender specific biomarker system for clinical screening to detect the risk of the potential development or progression of a tumor.

Research conclusions

Results give new insight into how environment interacts with cell metabolism and redox immune state to influence Th cell differentiation and functions. Furthermore, the mechanisms of degenerative processes that compromise redox immune function have been explained. Results support the goals of translational medicine that tries to promote personalized strategies for the prevention and treatment of cancer.

Research perspectives

Trx1/CD30 and selected biomarkers can be used for new personalized resolving treatments to target age-related immune decline, CRC onset and/or its progression. This will permit to select novel therapies. Given the retrospective nature of this study, additional research with larger prospective clinical trials is necessary to assess the impact of Trx1/CD30 for the treatment.