Efficacy of Cancer Antigen 15-3, Trefoil Factor-3, and Human Epididymis Protein-4 in the Diagnosis of Breast Cancer Cancer antigens in BC
Abstract
Background: Breast cancer (BC) is a significant global health concern, and delayed or frequently inadequate diagnosis has led to fatalities in many women. Consequently, research is needed to evaluate novel biomarkers for BC detection and monitoring. The current study aimed to assess the effectiveness of Cancer Antigen 15-3 (CA15-3), Trefoil Factor-3 (TFF3), and Human Epididymis Protein-4 (HE4) in diagnosing and monitoring BC.
Methods: The present case-control study recruited 72 women with BC, who were categorized into pre-treatment (n=15) and post-treatment with chemotherapy involving anthracycline, cyclophosphamide, and docetaxel (n=57). Additionally, 15 healthy women served as controls. Serum levels of these biomarkers were measured at Al-Sadder Teaching Hospital in Iraq, using COBAS Integra 400 Plus for CA15-3 and enzyme-linked immunosorbent assay (ELISA) for TFF3 and HE4.
Results: Statistical analysis revealed significantly elevated CA15-3 and TFF3 levels in pre-treatment and post-treatment groups compared to controls (P<0.0001), with CA15-3 increasing from 10.27±2.89 U/mL (controls) to 63.3±19.24 U/mL (pre-treatment) and TFF3 from 4.73±0.97 pg/mL to 1811.0±155 pg/mL. The HE4 levels remained consistent across all groups (P=0.409).
Conclusion: These results support the use of CA15-3 and TFF3 as complementary biomarkers for BC management, particularly in tracking treatment response and disease recurrence.
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References
Sung VYC, Knight JF, Johnson RM, et al. Co-dependency for MET and FGFR1 in basal triple-negative breast cancers. NPJ Breast Cancer. 2021;7(1):36. doi:10.1038/s41523-021-00238-4.
Sharma R, Nanda M, Fronterre C, et al. Mapping cancer in Africa: a comprehensive and comparable characterization of 34 cancer types using estimates from GLOBOCAN 2020. Front public Heal. 2022;10:839835. doi:10.3389/fpubh.2022.839835.
Sha R, Kong X-M, Li X-Y, Wang Y-B. Global burden of breast cancer and attributable risk factors in 204 countries and territories, from 1990 to 2021: results from the Global Burden of Disease Study 2021. Biomark Res. 2024;12(1):87. doi:10.1186/s40364-024-00631-8.
Cao W, Qin K, Li F, Chen W. Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN). J Natl Cancer Cent. 2024;4(2):128-134. doi:10.1016/j.jncc.2024.05.001.
Li J, Guan X, Fan Z, et al. Non-invasive biomarkers for early detection of breast cancer. Cancers (Basel). 2020;12(10):2767. doi:10.3390/cancers12102767.
Araz M, Beypinar I, Kazan S, Inci F, Celiker M, Uysal M. Are preoperative serum CA15-3 levels different in breast cancer subgroups? Curr Probl Cancer. 2019;43(2):115-122. doi:10.1016/j.currproblcancer.2018.06.011.
Uygur MM, Gümüş M. The utility of serum tumor markers CEA and CA 15–3 for breast cancer prognosis and their association with clinicopathological parameters. Cancer Treat Res Commun. 2021;28:100402. doi:10.1016/j.ctarc.2021.100402.
Loric S, Denis JA, Desbene C, Sabbah M, Conti M. Extracellular vesicles in breast cancer: from biology and function to clinical diagnosis and therapeutic management. Int J Mol Sci. 2023;24(8):7208. doi:10.3390/ijms24087208.
Hoffmann W. Trefoil factor family (Tff) peptides and their links to inflammation: A re-evaluation and new medical perspectives. Int J Mol Sci. 2021;22(9):4909. doi:10.3390/ijms22094909.
Hoffmann W. Trefoil factor family (TFF) peptides and their diverse molecular functions in mucus barrier protection and more: changing the paradigm. Int J Mol Sci. 2020;21(12):4535. doi:10.3390/ijms21124535
Yang Y, Lin Z, Lin Q, Bei W, Guo J. Pathological and therapeutic roles of bioactive peptide trefoil factor 3 in diverse diseases: recent progress and perspective. Cell Death Dis. 2022;13(1):62. doi:10.1038/s41419-022-04504-6.
Taniguchi Y, Kurokawa Y, Takahashi T, et al. Prognostic Value of Trefoil Factor 3 Expression in Patients with Gastric Cancer. World J Surg. 2018;42:3997-4004. doi:10.1007/s00268-018-4737-0.
Huang Y-G, Li Y-F, Wang L-P, Zhang Y. Aberrant expression of trefoil factor 3 is associated with colorectal carcinoma metastasis. J Cancer Res Ther. 2013;9(3):376-380. doi:10.4103/0973-1482.119308.
Lau W-H, Pandey V, Kong X, et al. Trefoil factor-3 (TFF3) stimulates de novo angiogenesis in mammary carcinoma both directly and indirectly via IL-8/CXCR2. PLoS One. 2015;10(11):e0141947. doi:10.1371/journal.pone.0141947.
Nørgaard M, Haldrup C, Storebjerg TM, et al. Comprehensive evaluation of TFF3 promoter hypomethylation and molecular biomarker potential for prostate cancer diagnosis and prognosis. Int J Mol Sci. 2017;18(9):2017. doi:10.3390/ijms18092017.
Wahab MRA, Palaniyandi T, Viswanathan S, et al. Biomarker-specific biosensors revolutionise breast cancer diagnosis. Clin Chim Acta. 2024;555:117792. doi:10.1016/j.cca.2024.117792.
Huang P, Wolde T, Bhardwaj V, Zhang X, Pandey V. TFF3 and PVRL2 co-targeting identified by multi-omics approach as an effective cancer immunosuppression strategy. Life Sci. 2024;357:123113. doi:10.1016/j.lfs.2024.123113.
Anastasi E, Farina A, Granato T, et al. Recent insight about HE4 role in ovarian cancer oncogenesis. Int J Mol Sci. 2023;24(13):10479. doi:10.3390/ijms241310479.
Elorriaga MÁ, Neyro JL, Mieza J, Cristóbal I, Llueca A. Biomarkers in ovarian pathology: from screening to diagnosis. Review of the literature. J Pers Med. 2021;11(11):1115. doi:10.3390/jpm11111115.
Mais V, Fais ML, Peiretti M, et al. HE4 tissue expression as a putative prognostic marker in low-risk/low-grade endometrioid endometrial cancer: a review. Curr Oncol. 2022;29(11):8540-8555. doi:10.3390/curroncol29110673.
Abas A-SM, Sherif MH, Elmoneam Farag SA. Diagnostic and prognostic role of serum omentin and NGAL levels in Egyptian breast cancer patients. Int J Breast Cancer. 2022;2022(1):5971981. doi:10.1155/2022/5971981.
Li X, Dai D, Chen B, Tang H, Xie X, Wei W. Determination of the prognostic value of preoperative CA15-3 and CEA in predicting the prognosis of young patients with breast cancer. Oncol Lett. 2018;16(4):4679-4688. doi:10.3892/ol.2018.9160.
Hing JX, Mok CW, Tan PT, et al. Clinical utility of tumour marker velocity of cancer antigen 15–3 (CA 15–3) and carcinoembryonic antigen (CEA) in breast cancer surveillance. The Breast. 2020;52:95-101. doi:10.1016/j.breast.2020.05.005.
Fu Y, Li H. Assessing clinical significance of serum CA15-3 and carcinoembryonic antigen (CEA) levels in breast cancer patients: a meta-analysis. Med Sci Monit Int Med J Exp Clin Res. 2016;22:3154. doi: 10.12659/MSM.896563.
Seale KN, Tkaczuk KHR. Circulating biomarkers in breast cancer. Clin Breast Cancer. 2022;22(3):e319-e331. doi:10.1016/j.clbc.2021.09.006.
Taghizadeh A, Pourali L, Joudi M, et al. Assessment of elevated serum tumor markers carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) among patients with different subtypes of metastatic breast cancer. Middle East J Cancer. 2019;10(1):17-22. doi:10.30476/mejc.2019.44681.
Lian M, Zhang C, Zhang D, et al. The association of five preoperative serum tumor markers and pathological features in patients with breast cancer. J Clin Lab Anal. 2019;33(5):e22875. doi:10.1002/jcla.22875.
AbdelFattah M, Abdallah AZ, Gabr AG, Mohammed DA, Roshdy YA, Mohammed AH, et al. Clinical Significance of Serum Cancer Antigen 15-3 (CA15-3) as Prognostic Parameter in Non-metastatic Breast Cancer Patients: is still a valid test?. The Egyptian Journal of Hospital Medicine (April 2024), 95, 2001-2006. doi:10.21608/ejhm.2024.357745.
Ryu JM, Kang D, Cho J, et al. Prognostic impact of elevation of cancer antigen 15-3 (CA15-3) in patients with early breast cancer with normal serum CA15-3 level. J Breast Cancer. 2023;26(2):126. doi:10.4048/jbc.2023.26.e17.
Gupta SK, Kumar V, Anees A, Goel A. The study of prognostic significance of CA 15-3 in breast cancer. Int Surg J, 5(2), 580. doi:10.18203/2349-2902.isj20180356.
Li J, Liu L, Feng Z, et al. Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study. Breast Cancer. 2020;27:621-630. doi:10.1007/s12282-020-01058-3.
Coppola L, Cianflone A, Pane K, Franzese M, Mirabelli P, Salvatore M. The impact of different preanalytical methods related to CA 15-3 determination in frozen human blood samples: a systematic review. Syst Rev. 2021;10(1):102. doi:10.1186/s13643-021-01631-7.
Kabir RJ, Mahmud R, Kabir ME, et al. Diagnostic Accuracy of Cancer Antigen 15-3 as a Seromarker Among Recurrent Breast Carcinoma in Bangladesh. Cureus. 2024;16(9):e68448. doi:10.7759/cureus.68448.
Abdelrazek MA, Nageb A, Barakat LA, Abouzid A, Elbaz R. BC-DETECT: combined detection of serum HE4 and TFF3 improves breast cancer diagnostic efficacy. Breast Cancer. 2022;29(3):507-515. doi:10.1007/s12282-021-01328-8.
Huang P, Li F, Li L, et al. lncRNA profile study reveals the mRNAs and lncRNAs associated with docetaxel resistance in breast cancer cells. Sci Rep. 2018;8(1):17970. doi:10.1038/s41598-018-36231-4.
Wu J-R, Zhao Y, Zhou X-P, Qin X. Estrogen receptor 1 and progesterone receptor are distinct biomarkers and prognostic factors in estrogen receptor-positive breast cancer: Evidence from a bioinformatic analysis. Biomed Pharmacother. 2020;121:109647. doi:10.1016/j.biopha.2019.109647.
Wang Q, Jiang Y, Du M, Yang L, Yuan Q. Association of functional genetic variants in TFF1 and nephrolithiasis risk in a Chinese population. BMC Urol. 2022;22(1):127. doi:10.1186/s12894-022-01081-w.
May FEB, Westley BR. TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer. Endocr Relat Cancer. 2015;22(3):465. doi: 10.1530/ERC-15-0129.
Shen M, Yang L, Lei T, et al. Correlation between CA12 and TFF3 and their prediction value of neoadjuvant chemotherapy response in breast cancer. J Clin Pharm Ther. 2022;47(5):609-618. doi:10.1111/jcpt.13580.
Yan S, Yue S. Identification of early diagnostic biomarkers for breast cancer through bioinformatics analysis. Medicine (Baltimore). 2023;102(37):e35273. doi: 10.1097/MD.0000000000035273.
Zhang Y, Liu Y, Wang L, Song H. The expression and role of trefoil factors in human tumors. Transl Cancer Res. 2019;8(4):1609. doi: 10.21037/tcr.2019.07.48.
Baba KSSS, Rehman MA, Kumar JP, et al. Serum human epididymis protein-4 (HE4)-a novel approach to differentiate malignant from benign breast tumors. Asian Pacific J cancer Prev APJCP. 2021;22(8):2509. doi: 10.31557/APJCP.2021.22.8.2509.
Zhu L, Zhuang H, Wang H, et al. Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer. Oncotarget. 2015;7(1):729. doi: 10.18632/oncotarget.6327.
Namini NM, Abdollahi A, Movahedi M, Razavi AE, Saghiri R. HE4, a new potential tumor marker for early diagnosis and predicting of breast cancer progression. Iran J Pathol. 2021;16(3):284. doi: 10.30699/IJP.2021.135323.2482.
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