Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Diagnostic and differential efficacy of cyclin D1 and CA15-3 in breast cancer and benign breast tumors

Anmar R. Raheem1,2, Omar F. Abdul-Rasheed1*, Omar S. Khattab3, Ahmed Z. Abdulhameed4, Hussein A. Abid1,5*

+ Author Affiliations

Journal of Angiotherapy 7(1) 1-6 https://doi.org/10.25163/angiotherapy.717335

Submitted: 19 April 2023  Revised: 16 July 2023  Published: 23 July 2023 

Abstract


Background: Cyclin D1 promotes cancer cell proliferation and is associated with tamoxifen-resistance in breast cancer. The cancer antigen 15-3, CA15-3, was reported to stimulate the body’s defense system, but its role in early breast cancer detection remains unclear. Thus, this study sought to investigate the diagnostic and differential utility of cyclin D1 and CA15-3 in breast cancer and benign breast tumors. The study was conducted between April 2022 and January 2023, including 30 breast cancer patients, 30 benign breast tumor patients, and 60 controls. Serum cyclin D1 and CA15-3 levels were measured by ELISA. Receiver operating characteristic curves used to assess the diagnostic performance of each marker. Results: Serum CA15-3 levels were significantly higher in breast cancer patients (38.89±8.63 U/mL) compared to patients with benign breast tumors (32.64±8.47 U/mL) and healthy controls (21.07±8.49 U/mL). In addition, the benign breast tumor group had markedly higher CA15-3 levels than controls. Serum cyclin D1 concentrations differed significantly between the three study groups: 0.85±0.15 ng/mL in breast cancer patients, 0.97±0.21 ng/mL in  the benign  tumor  group,  and   0.56±0.14  ng/mL  in   healthy controls. Conclusion: Elevated cyclin D1 levels were found in breast tumors, suggesting its possible use as a routine diagnostic test. CA15-3 demonstrated the highest levels in breast cancer patients, indicating usefulness for diagnosis and screening.

Keywords: Breast cancer; early detection; diagnostic accuracy; tumor biomarkers

References


Amin, M.B., Greene, F.L., Edge, S.B., Compton, C.C., Gershenwald, J.E., Brookland, R.K., Meyer, L., Gress, D.M., Byrd, D.R., Winchester, D.P., 2017. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA. Cancer J. Clin. 67, 93–99. https://doi.org/10.3322/caac.21388

Bahramy, A., Zafari, N., Rajabi, F., Aghakhani, A., Jayedi, A., Khaboushan, A.S., Zolbin, M.M., Yekaninejad, M.S., 2023. Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis. Front. Mol. Biosci. 10. https://doi.org/10.3389/fmolb.2023.1096524

Bièche, I., Olivi, M., Noguès, C., Vidaud, M., Lidereau, R., 2002. Prognostic value of CCND1 gene status in sporadic breast tumours, as determined by real-time quantitative PCR assays. Br. J. Cancer 86, 580–586. https://doi.org/10.1038/sj.bjc.6600109

Caldon, C.E., Musgrove, E.A., 2010. Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer. Cell Div. https://doi.org/10.1186/1747-1028-5-2

Casimiro, M.C., Crosariol, M., Loro, E., Li, Z., Pestell, R.G., 2012. Cyclins and cell cycle control in cancer and disease. Genes Cancer 3, 649–657. https://doi.org/10.1177/1947601913479022

Chang, M., 2012. Tamoxifen resistance in breast cancer. Biomol. Ther. 20, 256–267. https://doi.org/10.4062/biomolther.2012.20.3.256

Dai, X., Li, T., Bai, Z., Yang, Y., Liu, X., Zhan, J., Shi, B., 2015. Breast cancer intrinsic subtype classification, clinical use and future trends. Am. J. Cancer Res. 5, 2929–43.

DeSantis, C.E., Ma, J., Gaudet, M.M., Newman, L.A., Miller, K.D., Goding Sauer, A., Jemal, A., Siegel, R.L., 2019. Breast cancer statistics, 2019. CA. Cancer J. Clin. 69, 438–451. https://doi.org/10.3322/caac.21583

Duffy, M.J., Shering, S., Sherry, F., McDermott, E., O’Higgins, N., 2000. CA 15–3: A Prognostic Marker in Breast Cancer. Int. J. Biol. Markers 15, 330–333. https://doi.org/10.1177/172460080001500410

Elsheikh, S., Green, A.R., Aleskandarany, M.A., Grainge, M., Paish, C.E., Lambros, M.B.K., Reis-Filho, J.S., Ellis, I.O., 2008. CCND1 amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome. Breast Cancer Res. Treat. https://doi.org/10.1007/s10549-007-9659-8

Jäger, W., Eibner, K., Löffler, B., Gleixner, S., Krämer, S., 2000. Serial CEA and CA 15-3 measurements during follow-up of breast cancer patients, in: Anticancer Research.

Khan, N.A.J., Abdallah, M., Tirona, M.T., 2021. Hormone receptor positive/HER2 negative breast cancer with isolated bladder metastasis: A rare case. J. Investig. Med. High Impact Case Reports 9, 232470962110221. https://doi.org/10.1177/23247096211022186

Lawicki, S., Zajkowska, M., Glazewska, E., Bedkowska, G., Szmitkowski, M., 2016. Plasma levels and diagnostic utility of VEGF, MMP-9, and TIMP-1 in the diagnosis of patients with breast cancer. Onco. Targets. Ther. 911. https://doi.org/10.2147/OTT.S99959

Li, Z., Wei, H., Li, S., Wu, P., Mao, X., 2022. The role of progesterone receptors in breast cancer. Drug Des. Devel. Ther. https://doi.org/10.2147/DDDT.S336643

Li, Z., Zou, W., Zhang, J., Zhang, Y., Xu, Q., Li, S., Chen, C., 2020. Mechanisms of CDK4/6 inhibitor resistance in luminal breast cancer. Front. Pharmacol. 11. https://doi.org/10.3389/fphar.2020.580251

Lian, M., Zhang, C., Zhang, D., Chen, P., Yang, H., Yang, Y., Chen, S., Hong, G., 2019. The association of five preoperative serum tumor markers and pathological features in patients with breast cancer. J. Clin. Lab. Anal. https://doi.org/10.1002/jcla.22875

Marrugo-Ramírez, J., Mir, M., Samitier, J., 2018. Blood-based cancer biomarkers in liquid biopsy: A promising non-invasive alternative to tissue biopsy. Int. J. Mol. Sci. 19, 2877. https://doi.org/10.3390/ijms19102877

Mohammedi, L., Doula, F.D., Mesli, F., Senhadji, R., 2019. Cyclin D1 overexpression in algerian breast cancer women: Correlation with CCND1 amplification and clinicopathological parameters. Afr. Health Sci. https://doi.org/10.4314/ahs.v19i2.38

Musgrove, E.A., Sutherland, R.L., 2009. Biological determinants of endocrine resistance in breast cancer. Nat. Rev. Cancer 9, 631–43. https://doi.org/10.1038/nrc2713

Rasmy, A., Abozeed, W., Elsamany, S., Baiomy, M. El, Nashwa, A., Amrallah, A., Hasaan, E., Alzahrani, A., Faris, M., Alsaleh, K., AlFaraj, A., 2016. Correlation of preoperative Ki67 and serum CA15.3 levels with outcome in early breast cancers a multi institutional study. Asian Pacific J. Cancer Prev. 17, 3595–600.

Seale, K.N., Tkaczuk, K.H.R., 2022. Circulating biomarkers in breast cancer. Clin. Breast Cancer 22, e319–e331. https://doi.org/10.1016/j.clbc.2021.09.006

Shaath, H., Elango, R., Alajez, N.M., 2021. Molecular classification of breast cancer utilizing long non-coding RNA (lncRNA) transcriptomes identifies novel diagnostic lncRNA panel for triple-negative breast cancer. Cancers (Basel). 13, 5350. https://doi.org/10.3390/cancers13215350

Smart, C.R., 1997. Limitations of the randomized trial for the early detection of cancer. Cancer 79, 1740–1746. https://doi.org/10.1002/(SICI)1097-0142(19970501)79:9<1740::AID-CNCR16>3.0.CO;2-Y

Sturgeon, C.M., Duffy, M.J., Stenman, U.-H., Lilja, H., Bru¨nner, N., Chan, D.W., Babaian, R., Bast, R.C., Dowell, B., Esteva, F.J., Haglund, C., Harbeck, N., Hayes, D.F., Holten-Andersen, M., Klee, G.G., Lamerz, R., Looijenga, L.H., Molina, R., Nielsen, H.J., Rittenhouse, H., Semjonow, A., Shih, I.-M., Sibley, P., So¨le´tormos, G., Stephan, C., Sokoll, L., Hoffman, B.R., Diamandis, E.P., 2008. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin. Chem. 54, e11–e79. https://doi.org/10.1373/clinchem.2008.105601

Tampellini, M., Berruti, A., Bitossi, R., Gorzegno, G., Alabiso, I., Bottini, A., Farris, A., Donadio, M., Sarobba, M.G., Manzin, E., Durando, A., Defabiani, E., De Matteis, A., Ardine, M., Castiglione, F., Danese, S., Bertone, E., Alabiso, O., Massobrio, M., Dogliotti, L., 2006. Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients. Breast Cancer Res. Treat. 98, 241–248. https://doi.org/10.1007/s10549-005-9155-y

Tarighati, E., Keivan, H., Mahani, H., 2022. A review of prognostic and predictive biomarkers in breast cancer. Clin. Exp. Med. https://doi.org/10.1007/s10238-021-00781-1

Tchakarska, G., Sola, B., 2020. The double dealing of cyclin D1. Cell Cycle. https://doi.org/10.1080/15384101.2019.1706903

Vaz-Luis, I., Winer, E.P., Lin, N.U., 2013. Human epidermal growth factor receptor-2-positive breast cancer: does estrogen receptor status define two distinct subtypes? Ann. Oncol. 24, 283–291. https://doi.org/10.1093/annonc/mds286

Wang, L., 2017. Early diagnosis of breast cancer. Sensors 17, 1572. https://doi.org/10.3390/s17071572

Xue, F., Meng, Y., Jiang, J., 2022. Diagnostic value of dynamic enhanced magnetic resonance imaging combined with serum CA15-3, CYFRA21-1, and TFF1 for breast cancer. J. Healthc. Eng. 2022, 1–6. https://doi.org/10.1155/2022/7984591

Yao, H., He, G., Yan, S., Chen, C., Song, L., Rosol, T.J., Deng, X., 2017. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget 8, 1913–1924. https://doi.org/10.18632/oncotarget.12284

Zhang, L., Huang, Y., Feng, Z., Wang, X., Li, H., Song, Fangfang, Liu, L., Li, J., Zheng, H., Wang, P., Song, Fengju, Chen, K., 2019. Comparison of breast cancer risk factors among molecular subtypes: A case-only study. Cancer Med. https://doi.org/10.1002/cam4.2012

Zhao, M., 2014. Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer. World J. Clin. Oncol. 5, 248. https://doi.org/10.5306/wjco.v5.i3.248

Full Text
Export Citation

View Dimensions


View Plumx



View Altmetric



0
Save
0
Citation
721
View
0
Share