The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer

Abstract Background There is a long-time unmet need for a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, a blood-based diagnostic can complement mammography and assist in the accurate detection of BC in the diagnostic process peri...

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Main Authors: Youn Ju Lee, Young Kim, Bo Bae Choi, Je Ryong Kim, Hye Mi Ko, Kyoung Hoon Suh, Jin Sun Lee
Format: Article
Language:English
Published: BMC 2022-01-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-021-09055-1
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author Youn Ju Lee
Young Kim
Bo Bae Choi
Je Ryong Kim
Hye Mi Ko
Kyoung Hoon Suh
Jin Sun Lee
author_facet Youn Ju Lee
Young Kim
Bo Bae Choi
Je Ryong Kim
Hye Mi Ko
Kyoung Hoon Suh
Jin Sun Lee
author_sort Youn Ju Lee
collection DOAJ
description Abstract Background There is a long-time unmet need for a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, a blood-based diagnostic can complement mammography and assist in the accurate detection of BC in the diagnostic process period of early diagnosis. 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 to identify BC by testing sera from biopsy-confirmed cancer patients and women without cancer. 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 women without cancer (n = 114), as well as in serum from 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 and classified by the subjects’ age and cancer stage. In addition to the Trx1 levels of BC patients, several pathological and molecular aspects of BC were analyzed. Test results were retrospectively 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 women without cancer was 5.45 ± 4.16 (±SD) ng/ml, that of the other malignant cancer patient group was 2.70 ± 2.01 ng/ml, and that from the BC group was 21.96 ± 6.79 ng/ml. The difference among these values was large enough to distinguish BC sera from non-BC control sera with a sensitivity of 97.17% and specificity of 94.15% (AUC 0.990, p < 0.0001). Most Trx1 levels from BC patients’ sera were higher than the cut-off value of 11.4 ng/ml regardless of age, stage, histological grade, type, and specific receptors’ expression profile of BC. The level of Trx1 could rescue women from most cases of misread or incomplete mammography diagnoses. Conclusion These results indicated that the blood level of Trx1 could be an effective and accurate means to assist the detection of BC during the early diagnosis period.
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spelling doaj.art-8469317436194c74aa78ed4189cb01042022-12-21T17:49:30ZengBMCBMC Cancer1471-24072022-01-0122111410.1186/s12885-021-09055-1The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancerYoun Ju Lee0Young Kim1Bo Bae Choi2Je Ryong Kim3Hye Mi Ko4Kyoung Hoon Suh5Jin Sun Lee6Department of Surgery, Chungnam National University Sejong HospitalE&S HealthcareDepartment of Radiology, Chungnam National University HospitalDepartment of Surgery, Chungnam National University HospitalDepartment of Surgery, Chungnam National University HospitalE&S HealthcareDepartment of Surgery, Chungnam National University HospitalAbstract Background There is a long-time unmet need for a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, a blood-based diagnostic can complement mammography and assist in the accurate detection of BC in the diagnostic process period of early diagnosis. 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 to identify BC by testing sera from biopsy-confirmed cancer patients and women without cancer. 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 women without cancer (n = 114), as well as in serum from 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 and classified by the subjects’ age and cancer stage. In addition to the Trx1 levels of BC patients, several pathological and molecular aspects of BC were analyzed. Test results were retrospectively 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 women without cancer was 5.45 ± 4.16 (±SD) ng/ml, that of the other malignant cancer patient group was 2.70 ± 2.01 ng/ml, and that from the BC group was 21.96 ± 6.79 ng/ml. The difference among these values was large enough to distinguish BC sera from non-BC control sera with a sensitivity of 97.17% and specificity of 94.15% (AUC 0.990, p < 0.0001). Most Trx1 levels from BC patients’ sera were higher than the cut-off value of 11.4 ng/ml regardless of age, stage, histological grade, type, and specific receptors’ expression profile of BC. The level of Trx1 could rescue women from most cases of misread or incomplete mammography diagnoses. Conclusion These results indicated that the blood level of Trx1 could be an effective and accurate means to assist the detection of BC during the early diagnosis period.https://doi.org/10.1186/s12885-021-09055-1Thioredoxin 1Breast CancerDiagnosticsMammographySensitivitySpecificity
spellingShingle Youn Ju Lee
Young Kim
Bo Bae Choi
Je Ryong Kim
Hye Mi Ko
Kyoung Hoon Suh
Jin Sun Lee
The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
BMC Cancer
Thioredoxin 1
Breast Cancer
Diagnostics
Mammography
Sensitivity
Specificity
title The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
title_full The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
title_fullStr The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
title_full_unstemmed The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
title_short The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
title_sort blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer
topic Thioredoxin 1
Breast Cancer
Diagnostics
Mammography
Sensitivity
Specificity
url https://doi.org/10.1186/s12885-021-09055-1
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