Investigation of CD73 expression in Iraqi patient women with breast tumors
Main Article Content
Keywords
Breast Tumors, Ecto-5'-nucleotidase, CD73, Immunohistochemistry (IHC).
Abstract
Biomarkers that aid in the diagnosis, prognosis, and prediction of breast cancer are critical for early detection and effective disease management throughout treatment. Although preclinical studies suggest that 5-ectonucleotidase (CD73) could be a diagnostic marker in several types of cancer, it can be an appealing treatment strategy in some molecular subgroups of breast cancer. The aim of this study is to investigate the expression of CD73 in breast tumors (malignant and benign) in Iraqi patients using immunohistochemistry (IHC), as well as its correlation with clinicopathological characteristics. A total of eighty-nine samples of paraffin embedded tissue blocks of different breast tissue tumors (71 females and 18 were males) with their data in addition to eleven cases of healthy breast biopsies as a control were collected from public and private hospitals and health institutions in Baghdad. The findings of this task demonstrated substantial variations in the expression of CD73 between breast malignant, benign tumors and control groups (P < 0.001). CD73 expression was highest in 75.56% of malignant cases, while only 31.82% of benign cases showed positive expression of CD73. Furthermore, significant associations were found between CD73 with gender and histological types in benign cases and with (ER, PR, HER-2) negative and triple negative molecular subtypes in malignant cases. There were no significant variations in CD73 expression with other clinicopathological features. This allowed us to suggest that inhibiting CD73 could be an appealing treatment strategy in the TNBC subgroup.
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2. Alwan NAS, Tawfeeq FN, Mallah NAG. Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq. J
Contemp Med Sci. 2019;5:14–9. doi:10.22317/jcms.v5i1.544
3. Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: Risk factors, cancer stem cells,
signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018;5:77–106. doi:10.1016/j.gendis.2018.05.001
4. Hafez A, Mohamed H. Assessment of the Perception of Aesthetics and Smile Attractiveness among Dental and Health Students. Int J Oncol Res [Internet]. 2022 [cited 2022 Nov 16];5. Available from: https://clinmedjournals.org/articles/ijor/international-journal-of-oncology research-ijor-5-037.php?jid=ijor doi:10.23937/2643-4563/1710037
5. Hussein TA, Tamemi IAA. Micro RNA 145 as Biomarker for Breast cancer. Res J Pharm Technol. 2019;12:5923. doi: 10.5958/0974-
360X.2019.01027.8.
6. Suhail Y, Cain MP, Vanaja K, Kurywchak PA, Levchenko A, Kalluri R, et al. Systems Biology of Cancer Metastasis. Cell Syst. 2019;9:109–27.doi:10.1016/j.cels.2019.07.003
7. Alrawi N. A review on breast cancer in Iraq and future therapies insights. Baghdad J Biochem Appl Biol Sci. 2022;3:4–16.
doi:10.47419/bjbabs.v3i01.64
8. Green AR, Powe DG, Rakha EA, Soria D, Lemetre C, Nolan CC, et al. Identification of key clinical phenotypes of breast cancer using a
reduced panel of protein biomarkers. Br J Cancer. 2013;109:1886–94. doi:10.1038/bjc.2013.528
9. Jayashree V, Velraj M. Breast Cancer and various Prognostic Biomarkers for the diagnosis of the disease: A Review. Res J Pharm Technol. 2017;10:3211. doi: 10.5958/0974- 360X.2017.00570.4.
10. Iwamoto T, Kajiwara Y, Zhu Y, Iha S. Biomarkers of neoadjuvant/adjuvant chemotherapy for breast cancer. Chin Clin Oncol. 2020;9:27–27. doi:10.21037/cco.2020.01.06
11. Fisusi FA, Akala EO. Drug Combinations in Breast Cancer Therapy. Pharm Nanotechnol. 2019;7:3–23. doi:10.2174/2211738507666190122111224
12. Allard B, Allard D, Buisseret L, Stagg J. The adenosine pathway in immuno-oncology. Nat Rev Clin Oncol. 2020;17:611–29.
doi:10.1038/s41571-020-0382-2
13. Choi HR, Oh HK, Park SH, Jeong Y. Expression of CD73 is associated with tumor progression and intratumoral inflammation in breast cancer. Asia Pac J Clin Oncol. 2022;18:35–43. doi:10.1111/ajco.13450
14. Messaoudi N, Cousineau I, Arslanian E, Henault D, Stephen D, Vandenbroucke-Menu F, et al. Prognostic value of CD73 expression in resected colorectal cancer liver metastasis. OncoImmunology. 2020;9:1746138. doi:10.1080/2162402X.2020.1746138
15. Rocha P, Salazar R, Zhang J, Ledesma D, Solorzano JL, Mino B, et al. CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma. Cancer Immunol Immunother. 2021;70:1965–76. doi:10.1007/s00262-020-02820-4
16. Magaki S, Hojat SA, Wei B, So A, Yong WH. An Introduction to the Performance of Immunohistochemistry. In: Yong WH, editor.
Biobanking [Internet]. New York, NY: Springer New York; 2019 [cited 2022 Nov 16]. p. 289–98. Available from:
http://link.springer.com/10.1007/978-1-4939-8935-5_25 doi:10.1007/978-1-4939-8935-5_25
17. Ismail PA, Yousif AM. Diagnosis of Breast Cancer by some remarkable enzymes. Iraq Med J. 2021;5:101–3. doi:10.22317/imj.v5i3.1056
18. Wang R, Zhang Y, Lin X, Gao Y, Zhu Y. Prognositic value of CD73-adenosinergic pathway in solid tumor: A meta-analysis and
systematic review. Oncotarget. 2017;8:57327–36. doi:10.18632/oncotarget.16905
19. Gao Z, Dong K, Zhang H. The Roles of CD73 in Cancer. BioMed Res Int. 2014;2014:1–9. doi:10.1155/2014/460654
20. Jeong YJ, Oh HK, Choi HR, Park SH. Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer.
Diagnostics. 2020;10:939. doi:10.3390/diagnostics10110939
21. Wang L, Zhou X, Zhou T, Ma D, Chen S, Zhi X, et al. Ecto-5’-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells. J Cancer Res Clin Oncol. 2008;134:365–72. doi:10.1007/s00432-007-0292-z
22. de Araújo JB, Kerkhoff VV, de Oliveira Maciel SFV, de Resende E Silva DT. Targeting the purinergic pathway in breast cancer and its
therapeutic applications. Purinergic Signal. 2021;17:179–200. doi:10.1007/s11302-020-09760-9
23. Jiang T, Xu X, Qiao M, Li X, Zhao C, Zhou F, et al. Comprehensive evaluation of NT5E/CD73 expression and its prognostic significance in distinct types of cancers. BMC Cancer. 2018;18:267. doi:10.1186/s12885-018-4073-7
24. Falih Soliman N, Jasim Mohamad B. The Impact of CD37 Ectoenzyme Expression in Benign and Malignant Colorectal Tumors. Arch Razi Inst. Razi Vaccine & Serum Research Institute; 2022;77:2049–57. doi:10.22092/ari.2022.358611.2261
25. Monteiro I, Missiaglia E, Sciarra A, Santos JV, Bouilly J, Romero P, et al. CD73 expression in normal, hyperplastic, and neoplastic thyroid: a systematic evaluation revealing CD73 overexpression as a feature of papillary carcinomas. Virchows Arch. 2021;479:209–14.
doi:10.1007/s00428-021-03100-x
26. YU K, NI C, SONG X, YUAN H, SUN K. Expression of CD73 in breast cancer and the correlation with its clinicopathological features.
Chin J Clin Pharmacol Ther. 2017;22:551.
27. Cerbelli B, Botticelli A, Pisano A, Pernazza A, Campagna D, De Luca A, et al. CD73 expression and pathologic response to neoadjuvant
chemotherapy in triple negative breast cancer. Virchows Arch. 2020;476:569–76. doi:10.1007/s00428-019-02722-6
28. Hu S, Meng F, Yin X, Cao C, Zhang G. NT5E is associated with unfavorable prognosis and regulates cell proliferation and motility in gastric cancer. Biosci Rep. 2019;39:BSR20190101.doi:10.1042/BSR20190101
29. Montecino-Rodriguez E, Berent-Maoz B,Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest.
2013;123:958–65. doi:10.1172/JCI64096
30. Jeske SS, Schuler PJ, Doescher J, Theodoraki MN, Laban S, Brunner C, et al. Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma. Immun Ageing. 2020;17:3. doi:10.1186/s12979-020- 0174-7
31. Häusler SFM, Montalbán del Barrio I, Strohschein J, Anoop Chandran P, Engel JB, Hönig A, et al. Ectonucleotidases CD39 and
CD73 on OvCA cells are potent adenosinegenerating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell
function and NK cell cytotoxicity. Cancer Immunol Immunother. 2011;60:1405–18. doi:10.1007/s00262-011-1040-4
32. Azambuja JH, Gelsleichter NE, Beckenkamp LR, Iser IC, Fernandes MC, Figueiró F, et al. CD73 Downregulation Decreases In Vitro and In Vivo Glioblastoma Growth. Mol Neurobiol. 2019;56:3260–79. doi:10.1007/s12035-018- 1240-4
33. Ranjbar M, Ranjbar Z, Zahed M, Nikookar N. CD73 a novel marker for the diagnosis of benign and malignant salivary gland tumors. J Clin Exp Dent. 2019;0–0. doi:10.4317/jced.54918
34. Alcedo KP, Bowser JL, Snider NT. The elegant complexity of mammalian ecto-5′-nucleotidase (CD73). Trends Cell Biol. 2021;31:829–42. doi:10.1016/j.tcb.2021.05.008
35. Mitrović N, Dragić M, Zarić M, Drakulić D, Nedeljković N, Grković I. Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. Neurosci Lett. 2019;712:134474. doi:10.1016/j.neulet.2019.134474
36. Supernat A, Markiewicz A, Wełnicka-Jaśkiewicz M, Seroczyńska B, Skokowski J, Sejda A, et al. CD73 Expression as a Potential Marker of Good Prognosis in Breast Carcinoma. Appl Immunohistochem Mol Morphol. 2012;20:103–7. doi:10.1097/PAI.0b013e3182311d82
37. Tripathi A, Lin E, Xie W, Flaifel A, Steinharter JA, Stern Gatof EN, et al. Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma. J Immunother Cancer.2020;8:e001467. doi:10.1136/jitc-2020-001467
38. Zhou X, Zhi X, Zhou P, Chen S, Zhao F, Shao Z, et al. Effects of ecto-5’-nucleotidase on human breast cancer cell growth in vitro and in vivo. Oncol Rep. 2007;17:1341–6.
39. Iser IC, Andrade Mello P, Davies S, Souza Santos JF, Pilger DA, Buffon A, et al. A three‐ dimensional microenvironment alters CD73
expression in cervical cancer. Cell Biochem Funct. 2021;39:780–90. doi:10.1002/cbf.3649
40. Gao Z, Wang H, Lin F, Wang X, Long M, Zhang H, et al. CD73 promotes proliferation and migration of human cervical cancer cells
independent of its enzyme activity. BMC Cancer.2017;17:135. doi:10.1186/s12885-017-3128-5
41. Katsuta E, Tanaka S, Mogushi K, Shimada S, Akiyama Y, Aihara A, et al. CD73 as a therapeutic target for pancreatic neuroendocrine
tumor stem cells. Int J Oncol. 2016;48:657–69. doi:10.3892/ijo.2015.3299
42. Zhou L, Jia S, Chen Y, Wang W, Wu Z, Yu W, et al. The distinct role of CD73 in the progression of pancreatic cancer. J Mol Med Berl Ger. 2019;97:803–15. doi:10.1007/s00109-018- 01742-0
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Mar 13, 2023
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Raghdah Naser Mohsin, & Ban Jasim Mohamad. (2023). Investigation of CD73 expression in Iraqi patient women with breast tumors. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 240-257. https://doi.org/10.47750/jptcp.2023.30.03.026
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How to Cite
Raghdah Naser Mohsin, & Ban Jasim Mohamad. (2023). Investigation of CD73 expression in Iraqi patient women with breast tumors. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 240-257. https://doi.org/10.47750/jptcp.2023.30.03.026