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.
Highlights
The human cytosolic thioredoxin (Trx) contains a redox-active dithiol moiety in its conserved active-site sequence
Measurement of serum Trx1 level in patients with breast cancer and other cancers Trx1 levels in serum samples obtained from patients with breast cancer (BC), lung cancer (LC), kidney cancer (KC) and colorectal cancer (CRC) were assayed using ELISA, and the results were displayed as a scatter dot plot (Figure 2)
We suggest that the Trx1 blood test itself is reliable for diagnosing breast cancer or as a screening test for early detection of breast cancer, and that the combinational use of Trx1 with either Carcinoembryonic antigen (CEA) or Cancer antigen 15–3 (CA15-3) overcomes their problems encountered in diagnosis by the CEA or CA153 test alone
Summary
The human cytosolic thioredoxin (Trx) contains a redox-active dithiol moiety in its conserved active-site sequence. Function of Trx has been implicated in regulating cell proliferation, differentiation, and apoptosis. Organisms living under aerobic conditions are exposed to reactive oxygen species (ROS) such as superoxide anion (O2–), hydrogen peroxide (H2O2), and nitric oxide (NO), which are generated by redox metabolism, mainly in mitochondria. It has been demonstrated in vitro that ROS in small amounts participate in many physiological processes such as signal transduction, cell differentiation, apoptosis, and modulation of transcription factors [1,2,3,4]. ROS contribute to tumor progression by amplifying genomic instability and transformed cells use ROS signals to sustain proliferation [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
