Role of Resistin Mutations in Chemotherapy Resistance: A Computational Analysis in Iraqi Women with Breast Cancer

Khadija A. Sahan; Zahraa A. Sahan; Thualfiqar Gh. Turki

doi:10.32007/jfacmedbaghdad3148

المؤلفون

Khadija A. Sahan University of information technology and communications https://orcid.org/0009-0007-8467-2187
Zahraa A. Sahan College of Dentistry, Al Mustansiria University, Baghdad, Iraq https://orcid.org/0009-0004-3933-5227
Thualfiqar Gh. Turki Al-Qasim Green University-College of Biotechnology, Medical Biotechnology, Iraq. https://orcid.org/0009-0004-4674-2410

DOI:

https://doi.org/10.32007/jfacmedbaghdad3148

الكلمات المفتاحية:

سرطان الثدي، طفرات وراثية، تحليل حاسوبي

الملخص

ملخص البحث:

المقدمة: يعد سرطان الثدي أحد أكثر أنواع السرطان شيوعًا بين النساء، حيث تساهم عوامل وراثية وبيئية متعددة في تطور هذا المرض.

الطرق: هدفت الدراسة إلى تحليل بعض تعددات الأشكال النوكليوتيدية المفردة (SNPs) التي قد تضر ببنية ووظيفة بروتين الريزستين (RETN)، وهو أحد الأهداف المستخدمة في العلاج الكيميائي لسرطان الثدي. استخدمنا منهجيات حاسوبية متنوعة لتحديد الطفرات الضارة التي قد تؤثر على وظيفة البروتين وتتسبب في مقاومة العلاج الكيميائي لدى مرضى سرطان الثدي. شملت الأدوات الحاسوبية المستخدمة: Haploreg وRegulome DB وPolyPhen-2 وProtparam وSWISS-MODEL.

النتائج: كشفت النتائج أن الطفرات rs1862513 وrs3219175 وrs34788323 وrs3745367 تمثل تغيرات حرجة في بروتين الريزستين الطبيعي، والتي قد تساهم في مقاومة العلاج الكيميائي وبالتالي تطور سرطان الثدي. كما قدمت الدراسة نماذج ثلاثية الأبعاد للبروتين الطبيعي والمتحور.

الاستنتاج: وفقًا لتحليلنا الحاسوبي، قد تؤثر هذه الطفرات على مواقع ارتباط بعض عوامل النسخ (TFs)، مما قد يغير من طبيعة تفاعلها مع عوامل النسخ الأخرى والمنشطات الجزيئية.

المراجع

1. Alkashaf KH, Mohammed SI. Impact of Clinical Pharmacist Intervention on Chemotherapy Knowledge, Attitude, and Practice among Breast Cancer Women. J Fac Med Baghdad. 2024 Apr 1;66(1):103-9. https://doi.org/10.32007/jfacmedbagdad.6612221.

2. Alhadethy DM, Altameemi EK, Khalaf LA, Kamal AM. Pathological Nipple discharge: a comparison between breast ultrasound and mammography. J Fac Med Baghdad. 2021 May 11;63(1):18-23. https://doi.org/10.32007/jfacmedbagdad.6311813.

3. Jasim SS, Taha GI. Comparison between HSV-1 Ag detection techniques by ELISA and real-time PCR in breast cancer patients suffering from periodontitis. J Fac Med Baghdad. 2023 Oct 1;65(3):227-33. https://doi.org/10.32007/jfacmedbagdad.2105.

4. Muñoz-Palomeque A, Guerrero-Ramirez MA, Rubio-Chavez LA, Rosales-Gomez RC, Lopez-Cardona MG, Barajas-Avila VH, et al. Association of RETN and CAP1 SNPs, expression and serum resistin levels with breast cancer in Mexican women. Genetic testing and molecular biomarkers. 2018 Apr 1;22(4):209-17. https://doi.org/10.1089/gtmb.2017.0212.

5. Sahan KA, Aziz IH, Dawood SN, Al Qazzaz H. The role of resistin gene polymorphism in Iraqi breast cancer patients. Biomedicine. 2022 Dec 31;42(6):1296-300. https://doi.org/10.51248/.v42i6.2393.

6. Aziz MA, Akter T, Sarwar MS, Islam MS. The first combined meta‐analytic approach for elucidating the relationship of circulating resistin levels and RETN gene polymorphisms with colorectal and breast cancer. EJMHG. 2022 Mar 1;23(1):27. https://doi.org/10.1186/s43042-022-00240-w.

7. Farhan HM, Abougabal K, Ramadan ME, Darwish T, Eldeiry NA, Abdelkareem SA. Impacts of RETN genetic polymorphism on breast cancer development in Beni-Suef females, Egypt. Egypt. J. Immunol. 2023 Apr;30:37-46. https://doi.org/10.55133/eji.300204.

8. Elkhattabi L, Morjane I, Charoute H, Saile R, Barakat A. Computational screening and analysis of the functional and structural impact of SNPS of the human RETN gene associated to type 2 diabetes. Atherosclerosis. 2020 Dec 1;315:e199-200. https://doi.org/10.1016/j.atherosclerosis.2020.10.622.

9. PolyPhen-2. [2023 Jan 10]. Retrieved from http://genetics.bwh.harvard.edu/pph2.

10. Haploreg. [2023 Jan 10]. Retrieved from https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php.

11. SNPinfo. [2023 Jan 10]. National Institute of Environmental Health Sciences. Retrieved from https://snpinfo.niehs.nih.gov/.

12. RegulomeDB. [2023 Jan 10]. Retrieved from https://regulomedb.org/regulome-search/.

13. ExPASy. [2023 Jan 10]. Retrieved from http://www.expasy.org/.

14. Swiss-Model. [2023 Jan 10]. Retrieved from https://swissmodel.expasy.org/.

15. Deb A, Deshmukh B, Ramteke P, Bhati FK, Bhat MK. Resistin: A journey from metabolism to cancer. TRANON. 2021 Oct 1;14(10):101178. https://doi.org/10.1016/j.tranon.2021.10.

16. Issac RM, Saldanha P, Mathai JM, Mathews J, Mathews R, Kumari B, et al. Histopathological characterization of carcinoma breast with BRCA1/2 sequence variation in a tertiary care center in Kerala, South India. BBRJ. 2022 Jan 1;6(1):117-21. https://doi.org/10.4103/bbrj.bbrj_206_21.

17. Lu XJ. DSSR-enabled innovative schematics of 3D nucleic acid structures with PyMOL. Nucleic acids research. 2020 Jul 27;48(13):e74-. https://doi.org/10.1093/nar/gkaa426.

18. Capriotti E, Montanucci L, Profiti G, Rossi I, Giannuzzi D, Aresu L, et al.. Fido-SNP: the first webserver for scoring the impact of single nucleotide variants in the dog genome. Nucleic Acids Research. 2019 Jul 2;47(W1):W136-41. https://doi.org/10.1093/nar/gkz420.

19. Mohanta TK, Khan A, Hashem A, Abd_Allah EF, Al-Harrasi A. The molecular mass and isoelectric point of plant proteomes. BMC genomics. 2019 Dec;20:1-4.

https://doi.org/10.1186/s12864-019-5983-8.

20. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al.. SWISS-MODEL: homology modelling of protein structures and complexes. NAR. 2018 Jul 2;46(W1):W296-303. https://doi.org/10.1093/nar/gky427.

21. Sriram N, Mukherjee S, Sah MK. Gene expression profiling and protein-protein interaction analysis reveals the dynamic role of MCM7 in Alzheimer's disorder and breast cancer. 3 Biotech. 2022 Jul;12(7):146. https://doi.org/10.1007/s13205-022-03207-1.

22. Chi LA, Vargas MC. In silico design of peptides as potential ligands to resistin. Journal of molecular modeling. 2020 May;26:1-4. https://doi.org/10.1007/s00894-020-4338-3.

23. Sudan SK, Deshmukh SK, Poosarla T, Holliday NP, Dyess DL, Singh AP, et al.. Resistin: An inflammatory cytokine with multi-faceted roles in cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Dec 1;1874(2):188419. https://doi.org/10.1016/j.bbcan.2020.188419.

24. Sahan KA, Aziz IH, Dawood SN, Abdul Razzaq SS. The Effect of Genetic Polymorphism of Resistin Gene among Iraqi Breast Cancer Women. Iraqi journal of biotechnology. 2023; 22 (1), 1-7. 565-Article Text-881-1-10-20230703.pdf

25. Tripathi D, Kant S, Pandey S, Ehtesham NZ. Resistin in metabolism, inflammation, and disease. The FEBS journal. 2020 Aug;287(15):3141-9. https://doi.org/10.1111/febs.15322.

26. Lim SW, Tan KJ, Azuraidi OM, Sathiya M, Lim EC, Lai KS, Yap WS, Afizan NA. Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer. Scientific Reports. 2021 Dec 17;11(1):24206. https://doi.org/10.1038/s41598-021-03624-x.