COMPREHENSIVE ANALYSIS OF PDZD2 EXPRESSION AND REGULATORY MECHANISMS IN BREAST INVASIVE CARCINOMA: IMPLICATIONS FOR PROGNOSIS AND THERAPEUTIC TARGETING

Main Article Content

Shahid Ullah
Syed Meesam Raza
Alkuwaykibi M S
Hedib Alkoumi H Alrawili
Hafeezullah
Alruwaili A M
Jamal Muhammad Khan

Keywords

Breast Invasive Carcinoma, Diagnosis, Treatment

Abstract

The investigation focused on elucidating the role of PDZD2 expression and its regulatory mechanisms in Breast Invasive Carcinoma (BRCA). Employing the UALCAN database, PDZD2 expression analysis unveiled a significant down-regulation in cancerous cells compared to normal controls, suggesting its involvement in BRCA proliferation. Further dissecting PDZD2 expression across various parameters revealed consistent down-regulation in different cancer stages, racial groups, genders, and age categories within BRCA patients, indicative of its pivotal role in disease progression. Additionally, this study explored the promoter methylation status of PDZD2, revealing a significant divergence between BRCA samples and normal controls. Analyzing promoter methylation across different parameters uncovered dynamic variations, with distinct methylation patterns observed across cancer stages, racial groups, genders, and age groups. Survival analysis using the KM plotter tool demonstrated a significant correlation between PDZD2 expression levels and overall survival in BRCA patients, with low PDZD2 expression correlating with higher survival rates. Furthermore, mutational analysis using the cBioPortal platform revealed a mutation rate of 4% in BRCA samples, predominantly featuring amplifications, deep deletions, and some missense mutations in PDZD2. However, these genetic alterations were observed to have minimal impact on PDZD2 dysregulation in BRCA. Collectively, these findings emphasize the multifaceted involvement of PDZD2 in BRCA pathogenesis, emphasizing its potential as a prognostic biomarker and therapeutic target in BRCA management.

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References

1. Khalil T, Okla M, Al-Qahtani W, Ali F, Zahra M, Shakeela Q, et al. Tracing probiotic producing bacterial species from gut of buffalo (Bubalus bubalis), South-East-Asia. Brazilian Journal of Biology. 2022;84:e259094.
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. Zhang L, Sahar A, Li C, Chaudhary A, Yousaf I, Saeedah M, et al. A detailed multi-omics analysis of GNB2 gene in human cancers. Brazilian Journal of Biology. 2022;84:e260169.
4. 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.
5. Khan M, Hameed Y. Discovery of novel six genes-based cervical cancer-associated biomarkers that are capable to break the heterogeneity barrier and applicable at the global level. Journal of Cancer Research and Therapeutics. 2023.
6. Sharma GN, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res. 2010 Apr;1(2):109-26.
7. Bizuayehu HM, Dadi AF, Hassen TA, Ketema DB, Ahmed KY, Kassa ZY, et al. Global burden of 34 cancers among women in 2020 and projections to 2040: Population-based data from 185 countries/territories. International Journal of Cancer. 2024;154(8):1377-93.
8. Usman M, Hameed Y, Ahmad M. Does human papillomavirus cause human colorectal cancer? Applying Bradford Hill criteria postulates. ecancermedicalscience. 2020;14.
9. Freier TA. Isolation and characterization of unique cholesterol-reducing anaerobes: Iowa State University; 1991.
10. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018;68(6):394-424.
11. Ban KA, Godellas CV. Epidemiology of breast cancer. Surgical Oncology Clinics. 2014;23(3):409-22.
12. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(1):7-33.
13. Zeng X, Liu C, Yao J, Wan H, Wan G, Li Y, et al. Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications. Pharmacological research. 2021;163:105320.
14. Koren S, Bentires-Alj M. Breast tumor heterogeneity: source of fitness, hurdle for therapy. Molecular cell. 2015;60(4):537-46.
15. Thomas MK, Tsang SW, Yeung M-L, Leung PS, Yao K-M. The roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell mass. Current Protein and Peptide Science. 2009;10(1):30-6.
16. Yeung ML, Tam TS, Tsang AC, Yao KM. Proteolytic cleavage of PDZD2 generates a secreted peptide containing two PDZ domains. EMBO reports. 2003;4(4):412-8.
17. Ma RYM, Tam TSM, Suen AP, Yeung PML, Tsang SW, Chung SK, et al. Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells. The International Journal of Biochemistry & Cell Biology. 2006;38(5-6):1015-22.
18. Tam CW, Liu VWS, Leung WY, Yao K-M, Shiu SYW. The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53. Cancer letters. 2008;271(1):64-80.
19. Guerrero Schimpf ML, Figueroa ME. The Autocrine Secreted PDZD2 Functions As a Novel Tumor Suppressor in AML, Inducing Growth Inhibition and Cell Cycle Arrest. Blood. 2021;138(Supplement 1):3320-.
20. 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.
21. Tan WJ, Lai JC, Thike AA, Lim JCT, Tan SY, Koh VCY, et al. Novel genetic aberrations in breast phyllodes tumours: comparison between prognostically distinct groups. Breast Cancer Research and Treatment. 2014 2014/06/01;145(3):635-45.
22. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BV, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649-58.
23. 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. Oncology letters. 2019;18(4):3501-16.
24. Identification of Key Biomarkers for the Future Applications in Diagnostics and Targeted Therapy of Colorectal Cancer. Current Molecular Medicine. 2022.
25. 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.
26. Usman M, Hameed Y, Ahmad M. Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences. Biomedical and Biotechnology Research Journal (BBRJ). 2020;4(4):285-92.
27. Yen C-Y, Huang H-W, Shu C-W, Hou M-F, Yuan S-SF, Wang H-R, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer letters. 2016;373(2):185-92.
28. McCleary-Wheeler AL, Lomberk GA, Weiss FU, Schneider G, Fabbri M, Poshusta TL, et al. Insights into the epigenetic mechanisms controlling pancreatic carcinogenesis. Cancer letters. 2013;328(2):212-21.
29. Zhang J, Huang J, Chen Y, Yuan F, Zhang H, Yan F, et al. Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma. Scientific Reports. 2015;5(1):13750.
30. Entezari M, Taheriazam A, Orouei S, Fallah S, Sanaei A, Hejazi ES, et al. LncRNA-miRNA axis in tumor progression and therapy response: An emphasis on molecular interactions and therapeutic interventions. Biomedicine & Pharmacotherapy. 2022;154:113609.
31. Wang R, Zhao X, Liu J, Zhang C, YE X. Development of a five-gene signature as a novel prognostic marker in ovarian cancer. Neoplasma. 2019;66(3).
32. Nymark P, Guled M, Borze I, Faisal A, Lahti L, Salmenkivi K, et al. Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos‐and histology‐related changes in lung cancer. Genes, Chromosomes and Cancer. 2011;50(8):585-97.
33. García-Guede Á, Vera O, Ibáñez-de-Caceres I. When oxidative stress meets epigenetics: implications in cancer development. Antioxidants. 2020;9(6):468.
34. Laitinen VH, Akinrinade O, Rantapero T, Tammela TL, Wahlfors T, Schleutker J. Germline copy number variation analysis in Finnish families with hereditary prostate cancer. The Prostate. 2016;76(3):316-24.

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