The Blood level of Thioredoxin 1 as a Supporting Biomarker in the Detection of Breast Cancer [post]

Youn Ju Lee, Young Kim, Bo Bae Choi, Je Ryong Kim, Hye Mi Ko, Kyoung Hoon Suh, Jin Sun Lee
2021 unpublished
Background: It has been a long-time unmet need to have a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, thus, playing a role to reduce death from breast cancer, a blood-based diagnostic can complement mammography and assist in the accurate diagnosis of BC. We have previously reported the possible use of thioredoxin 1 (Trx1) in serum as a novel means to detect BC. In the present study, we validated the clinical utility of Trx1
more » ... cal utility of Trx1 to detect BC by testing sera from biopsy-confirmed cancer patients, and normal healthy people.Methods: We have generated monoclonal antibodies against Trx1 and developed an ELISA kit that can quantitate Trx1 in sera. The level of Trx1 was determined in each serum from normal healthy women (n=114), as well as patients with BC (n=106), and other types of cancers (n=74) including cervical, lung, stomach, colorectal, and thyroid cancer. The sera from BC patients were collected according to their age and cancer stage. Several pathological and molecular aspects of BC were analyzed along with the Trx1 levels of BC patients. Test results were compared to those from mammography. Each test was duplicated, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests.Results: The mean level of Trx1 from normal women's sera was 5.45±4.16 (±SD) U/ml and that from BC was 21.96±6.79 U/ml. The difference between these two values was large enough to distinguish BC sera from healthy sera with a sensitivity of 94.3% and specificity of 94.7% (AUC 0.985, p<0.0001). Most Trx1 levels from BC patients' sera were higher than the cut-off value of 14.13 Unit/ml regardless of age, stage, histological grade, type, and specific receptors' expression profile of BC. The blood levels of Trx1 from the group of patients with other types of cancers (2.70±2.01 U/ml) was low to be distinguishable from BC. Trx1 level could rescue most of misreading incompleteness of mammography. Conclusion: These results indicated that the blood level of Trx1 could be an effective and accurate means to assist or complement current BC diagnostic modalities.
doi:10.21203/rs.3.rs-165194/v1 fatcat:yg3a442gdndobe7kgu5fuaxxj4