EXPLORING THE ROLE OF ANKRD1 IN BREAST INVASIVE CARCINOMA: EXPRESSION ANALYSIS, PROMOTER METHYLATION, AND PROGNOSTIC IMPLICATIONS THROUGH BIOINFORMATICS ANALYSIS

Main Article Content

Muhammad Ejaz
Muhammad Jamil Yousaf
Hafeez Ullah
Asma Iqbal
Ahad Masood Hashmi
Junaid Farooq
Usama Tahir
Abdul Waheed Khan
Inam Ullah Khan
Syed Meesam Raza
Jamal Muhammad Khan

Keywords

ANKRD1, Cancer, Biomarker, Prognosis

Abstract

The present study deciphers the expression patterns and methylation status of ANKRD1, a potential biomarker, in breast invasive carcinoma (BRCA) using bioinformatics tools. Initially, ANKRD1 expression was analyzed in BRCA and normal control samples, revealing significant down-regulation in tumor samples compared to controls, indicating its potential role in BRCA progression. Subsequently, ANKRD1 expression was assessed across various clinical parameters, including cancer stages, patient demographics, and race. Notable discrepancies in ANKRD1 expression were observed across different cancer stages, genders, ages, and racial backgrounds of BRCA patients, emphasizing its clinical significance in BRCA pathogenesis. Promoter methylation analysis revealed significant hypo-methylation of ANKRD1 in BRCA samples compared to normal controls, suggesting potential epigenetic regulation of ANKRD1 expression in BRCA. Furthermore, survival analysis using the KM plotter tool demonstrated a significant correlation between ANKRD1 expression levels and patient survival outcomes, with high ANKRD1 expression associated with poor overall survival in BRCA patients. Mutational analysis revealed minimal genetic alterations in ANKRD1 in BRCA samples, suggesting that genetic variations have limited impact on ANKRD1 dysregulation in BRCA. These findings underscore the potential of ANKRD1 as a prognostic marker and therapeutic target in BRCA management.

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References

1. Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9:20503121211034366.
2. Yasir M, Nawaz A, Ghazanfar S, Okla M, Chaudhary A, Al WH, et al. Anti-bacterial activity of essential oils against multidrug-resistant foodborne pathogens isolated from raw milk. Brazilian Journal of Biology. 2022;84:e259449.
3. Hameed Y, Ejaz S. TP53 lacks tetramerization and N-terminal domains due to novel inactivating mutations detected in leukemia patients. Journal of Cancer Research and Therapeutics. 2021;17(4):931-7.
4. Usman M, Hameed Y, Ahmad M. Does human papillomavirus cause human colorectal cancer? Applying Bradford Hill criteria postulates. ecancermedicalscience. 2020;14.
5. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.
6. Ahmad M, Khan M, Asif R, Sial N, Abid U, Shamim T, et al. Expression characteristics and significant diagnostic and prognostic values of ANLN in human cancers. International Journal of General Medicine. 2022:1957-72.
7. Alkabban FM FT. Breast Cnacer. StatPearls. 2024.
8. Watanabe Y, Anan K. The decision to perform or omit sentinel lymph node biopsy during mastectomy for ductal carcinoma in situ should be tailored in accordance with preoperative findings. Breast Cancer. 2019 Mar;26(2):261-2.
9. Radovic N, Ivanac G, Divjak E, Biondic I, Bulum A, Brkljacic B. Evaluation of Breast Cancer Morphology Using Diffusion-Weighted and Dynamic Contrast-Enhanced MRI: Intermethod and Interobserver Agreement. J Magn Reson Imaging. 2019 May;49(5):1381-90.
10. Rocque GB, Williams CP, Kenzik KM, Jackson BE, Azuero A, Halilova KI, et al. Concordance with NCCN treatment guidelines: Relations with health care utilization, cost, and mortality in breast cancer patients with secondary metastasis. Cancer. 2018 Nov 1;124(21):4231-40.
11. Seroussi B, Lamy JB, Muro N, Larburu N, Sekar BD, Guézennec G, et al. Implementing Guideline-Based, Experience-Based, and Case-Based Approaches to Enrich Decision Support for the Management of Breast Cancer Patients in the DESIREE Project. Stud Health Technol Inform. 2018;255:190-4.
12. Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021;184(21):5309-37.
13. Xu W, Li H, Hameed Y, Abdel-Maksoud MA, Almutairi SM, Mubarak A, et al. Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma. Oncology Research. 2023;31(5):819.
14. Freier TA. Isolation and characterization of unique cholesterol-reducing anaerobes: Iowa State University; 1991.
15. Davidson S, Coles M, Thomas T, Kollias G, Ludewig B, Turley S, et al. Fibroblasts as immune regulators in infection, inflammation and cancer. Nat Rev Immunol. 2021 Nov;21(11):704-17.
16. Identification of Key Biomarkers for the Future Applications in Diagnostics and Targeted Therapy of Colorectal Cancer. Current Molecular Medicine. 2022.
17. Kojic S, Radojkovic D, Faulkner G. Muscle ankyrin repeat proteins: their role in striated muscle function in health and disease. Critical reviews in clinical laboratory sciences. 2011;48(5-6):269-94.
18. Ma G, Wang H, Gu X, Li W, Zhang X, Cui L, et al. CARP, a myostatin-downregulated gene in CFM cells, is a novel essential positive regulator of myogenesis. International Journal of Biological Sciences. 2014;10(3):309.
19. Miller MK, Bang M-L, Witt CC, Labeit D, Trombitas C, Watanabe K, et al. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. Journal of molecular biology. 2003;333(5):951-64.
20. Usman M, Hameed Y. GNB1, a novel diagnostic and prognostic potential biomarker of head and neck and liver hepatocellular carcinoma. Journal of Cancer Research and Therapeutics. 9000.
21. Mazzeo L, Ghosh S, Di Cicco E, Isma J, Tavernari D, Samarkina A, et al. ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation. Nature Communications. 2024 2024/02/03;15(1):1038.
22. Usman M, Ahmad M, Hameed Y, Ahmed H, Hussain MS, Ur J, et al. Identification of correlation between human papillomavirus and prostate cancer: Bradford Hill criteria based evaluation. 2021.
23. Jeyaseelan R, Poizat C, Baker RK, Abdishoo S, Isterabadi LB, Lyons GE, et al. A novel cardiac-restricted target for doxorubicin: CARP, a nuclear modulator of gene expression in cardiac progenitor cells and cardiomyocytes. Journal of Biological Chemistry. 1997;272(36):22800-8.
24. Yu F-X, Zhao B, Guan K-L. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163(4):811-28.
25. Dey A, Varelas X, Guan K-L. Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine. Nature Reviews Drug Discovery. 2020;19(7):480-94.
26. Kojic S, Nestorovic A, Rakicevic L, Belgrano A, Stankovic M, Divac A, et al. A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein. Archives of biochemistry and biophysics. 2010;502(1):60-7.
27. Park J-H, Liu L, Kim I-H, Kim J-H, You K-R, Kim D-G. Identification of the genes involved in enhanced fenretinide-induced apoptosis by parthenolide in human hepatoma cells. Cancer research. 2005;65(7):2804-14.
28. Scurr LL, Guminski AD, Chiew Y-E, Balleine RL, Sharma R, Lei Y, et al. Ankyrin repeat domain 1, ANKRD1, a novel determinant of cisplatin sensitivity expressed in ovarian cancer. Clinical cancer research. 2008;14(21):6924-32.
29. Takahashi A, Seike M, Chiba M, Takahashi S, Nakamichi S, Matsumoto M, et al. Ankyrin repeat domain 1 overexpression is associated with common resistance to afatinib and osimertinib in EGFR-mutant lung cancer. Scientific reports. 2018;8(1):14896.
30. Chen W, Bai Y, Patel C, Geng F. Autophagy promotes triple negative breast cancer metastasis via YAP nuclear localization. Biochemical and Biophysical Research Communications. 2019 2019/12/03/;520(2):263-8.
31. Kikuchi M, Yamashita K, Waraya M, Minatani N, Ushiku H, Kojo K, et al. Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget. 2016 Jan 12;7(2):1741-53.
32. Maciejczyk A, Szelachowska J, Czapiga B, Matkowski R, Hałoń A, Györffy B, et al. Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. J Histochem Cytochem. 2013 May;61(5):330-9.
33. Dong Y, Wu X, Xu C, Hameed Y, Abdel-Maksoud MA, Almanaa TN, et al. Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures. Aging. 2024;16(3):2591-616.
34. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017 Aug;19(8):649-58.
35. Jia B, Zhao X, Wang Y, Wang J, Wang Y, Yang Y. Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data. Oncol Lett. 2019 Oct;18(4):3501-16.
36. Hu H, Umair M, Khan SA, Sani AI, Iqbal S, Khalid F, et al. CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology. American Journal of Translational Research. 2024;16(2):432.
37. Abdel-Maksoud MA, Ullah S, Nadeem A, Shaikh A, Zia MK, Zakri AM, et al. Unlocking the diagnostic, prognostic roles, and immune implications of BAX gene expression in pan-cancer analysis. American Journal of Translational Research. 2024;16(1):63.
38. Maciejczyk A, Szelachowska J, Czapiga B, Matkowski R, Hałoń A, Györffy B, et al. Elevated BUBR1 expression is associated with poor survival in early breast cancer patients: 15-year follow-up analysis. Journal of Histochemistry & Cytochemistry. 2013;61(5):330-9.
39. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer discovery. 2012;2(5):401-4.
40. Yen CY, Huang HW, Shu CW, Hou MF, Yuan SS, Wang HR, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Lett. 2016 Apr 10;373(2):185-92.
41. Jiménez AP, Traum A, Boettger T, Hackstein H, Richter AM, Dammann RH. The tumor suppressor RASSF1A induces the YAP1 target gene ANKRD1 that is epigenetically inactivated in human cancers and inhibits tumor growth. Oncotarget. 2017 Oct 24;8(51):88437-52.
42. Usman M, Hameed Y, Ahmad M, Jalil Ur R, Ahmed H, Hussain MS, et al. Breast Cancer Risk and Human Papillomavirus Infection: A Bradford Hill Criteria Based Evaluation. Infect Disord Drug Targets. 2022;22(4):e200122200389.
43. Mao J, Huang X, Okla MK, Abdel-Maksoud MA, Mubarak A, Hameed Z, et al. Risk Factors for TERT Promoter Mutations with Papillary Thyroid Carcinoma Patients: A Meta-Analysis and Systematic Review. Comput Math Methods Med. 2022;2022:1721526.
44. Ullah L, Hameed Y, Ejaz S, Raashid A, Iqbal J, Ullah I, et al. Detection of novel infiltrating ductal carcinoma-associated BReast CAncer gene 2 mutations which alter the deoxyribonucleic acid-binding ability of BReast CAncer gene 2 protein. J Cancer Res Ther. 2020;16(6):1402-7.
45. Zhang L, Sahar AM, Li C, Chaudhary A, Yousaf I, Saeedah MA, et al. A detailed multi-omics analysis of GNB2 gene in human cancers. Braz J Biol. 2022;84:e260169.

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