Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

• Published in: World journal of gastrointestinal oncology Vol. 11; no. 2; pp. 117 - 138
• Main Authors: Berghella, Anna Maria, Aureli, Anna, Canossi, Angelica, Beato, Tiziana Del, Colanardi, Alessia, Pellegrini, Patrizia
• Format: Journal Article
• Language: English
• Published: China Baishideng Publishing Group Inc 15.02.2019
• Subjects: Retrospective Study; Aging and cancer biomarker; Cancer-related mechanisms; Oxidation and immune biomarkers; Cancer personalized treatments; Th cytokines; Trx1/CD30 target; KIRs and FcγR polymorphisms; Aging and disease
• ISSN: 1948-5204; 1948-5204
• DOI: 10.4251/wjgo.v11.i2.117

Identifying biomarkers for the risk of developing degenerative processes linked to aging and colorectal cancer (CRC) onset that could improve clinical strategies. To determine valid targets and a predictive biomarker's system of chronicization of inflammation for cancer treatment. 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-131 and FcγRIIIa-158 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". 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. 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.