Thioredoxin 1 as a serum marker for breast cancer and its use in combination with CEA or CA15-3 for improving the sensitivity of breast cancer diagnoses

Abstract

BackgroundThe human cytosolic thioredoxin (Trx) contains a redox-active dithiol moiety in its conserved active-site sequence. Activation by a wide variety of stimuli leads to secretion of this cytoplasmic protein. Function of Trx1 has been implicated in regulating cell proliferation, differentiation, and apoptosis. The aim of this study was to assess the clinical significance of serum Trx1 level in patients with breast carcinoma.ResultsTo clarify whether serum levels of Trx1 could be a serum marker for breast carcinoma, we measured the serum levels of Trx1 in patients with various carcinomas (breast, lung, colorectal, and kidney cancers) using an ELISA, and investigated its associations with the tumour grading from I to III. At the cut-off point 33.1725 ng/ml on the receiver operating characteristic curve (ROC) Trx1 could well discriminate breast carcinoma from normal controls with a sensitivity of 89.8%, specificity 78.0%, and area under the ROC (AUC) 0.901 ± 0.0252. The serum level was well correlated with the progress of the breast carcinoma. We also investigated the diagnostic capacity of CEA and CA15-3 for the early detection of metastatic breast cancer comparing that of Trx1. In contrast to the serum CEA and CA15-3 tumour markers, the serum Trx1 levels of the early cancer (grade I) patients were significantly higher than those of normal control subjects, showing a high diagnostic sensitivity and selectivity (89.4% sensitivity, and 72.0% specificity). The serum levels of Trx1 in various patients with lung, colorectal, and kidney carcinomas indicate that the level of Trx1 is significantly higher than those of other cancer patients. Combinational analysis of CEA or CA15-3 with Trx1 for the detection of breast cancer suggest that the diagnostic capacity of CEA or CA15-3 alone for the early detection of breast cancer, especially regarding sensitivity, is significantly improved by its combination with Trx1.ConclusionsTaken together, we conclude that serum Trx1 is useful for the early diagnosis of breast cancer or the early prediction prognosis of breast cancer, and therefore has a valuable use as a diagnostic marker and companion marker to CEA and CA15-3 for breast cancer.

Thioredoxin-1 and MMP-9 as biomarkers in breast cancer metastasis in Egyptian female patients

“…Trx-1 stimulates MMP-9 expression and promotes MMP-9 dependent invasion in breast cancer cells [12]. Thioredoxin system is highly expressed in breast tumors [23,24] and Trx-1 has been previously suggested as a suitable and diagnostic biomarker for breast cancer [8,13]. Our results extend these previous studies to show that Trx-1 level is significantly increased in breast cancer patients as compared to control.…”

“…One of the most important antioxidants is thioredoxin-1 (Trx-1), which is highly expressed in many tumors. A recent study showed increased level of serum Trx-1 in breast cancer patients in comparison with other cancers and normal persons [8]. Cellular redox homeostasis mediated by Trx-1 is required for activation of ribonucleotide reductase [9] and peroxiredoxins [10], induction of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) [11,12].…”

A Novel Strategy to Investigate Tissue‐Secreted Tumor Microenvironmental Proteins in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature

“…estimated the serum levels of thioredoxin1 (Trx1) in breast cancer patients using ELISA and confirmed its significantly elevated levels with high diagnostic sensitivity and specificity in GI samples. They also suggest that Trx1 combined with CEA and CA15‐3 significantly improved the sensitivity for the early detection of breast cancer with respect to grade . A study by Garczyk et al.…”

Evaluation of Thioredoxin-1 Serum Marker for Early Diagnosis of Primary Breast Cancer

“…hioredoxin-1 (TRX-1) is a low molecular weight redox protein found in both prokaryotic and eukaryotic cells 1. It activates specific nuclear transcription factors involved in gene decoding for production of substances that protect cells from oxidative stress induced by free oxygen radicals 2 . It has been proposed that serum TRX-1 may be a useful biomarker for early prediction of breast cancer, and higher levels have been found in sera of breast cancer patients 3 . An increase in the level of TRX-1 has been found to be associated with decreased T 20 https://doi.org/10.31386/dmj.2017.11.2.3…”