research-focus Research Focus International Scientific Journal Research Focus 2181-3833 Ilm-fan va innovatsiyalar akademiyasi 10.66073/researchfocus.v4i6.1712 REL-A-013036 14.00.00 SO‘LAK BEZLARI O‘SMALARINING PATOGENEZI VA MOLEKULAR-GENETIK JIHATLARI PATHOGENESIS AND MOLECULAR-GENETIC ASPECTS OF SALIVARY GLAND TUMORS ПАТОГЕНЕЗ И МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ АСПЕКТЫ ОПУХОЛЕЙ СЛЮННЫХ ЖЕЛЕЗ Ergashev Bekzod Jaloliddin o‘g‘li Central Asian Medical University xalqaro tibbiyot universiteti, O‘zbekiston, Farg‘ona, Burhoniddin Marg‘inoniy ko‘chasi 64 uy 06 07 2025 2025 4 6 274 281 https://creativecommons.org/licenses/by/4.0 Ushbu asar Creative Commons Attribution 4.0 International litsenziyasi asosida litsenziyalangan.

Ushbu maqolada so‘lak bezlari o‘smalarining rivojlanishiga asos bo‘luvchi molekulyar-genetik mexanizmlar tahlil qilinadi. Asosiy genetik mutatsiyalar (PLAG1, HMGA2, CTNNB1) va ularning o‘sma o‘sishiga ta‘siri ko‘rib chiqiladi. Karcinogenez jarayonida buzilgan signal uzatish yo‘llari (Wnt/β-katenin, PI3K/AKT/mTOR, NF-kB) ning roli yoritiladi. Molekulyar belgilarning (CK7, p40, p63, SOX10, S-100) ifodalanishiga va ularning diagnostik ahamiyatiga alohida e‘tibor qaratiladi. Surunkali yallig‘lanish va proinflammator sitokinlarning (IL-6, TNF-α) o‘sma rivojlanishiga ta‘siri muhokama qilinadi. Ushbu sharh maqola so‘lak bezlari o‘smalarini davolashga qaratilgan molekulyar nishonlarni aniqlash va yangi diagnostik va terapevtik strategiyalar ishlab chiqish zaruratini ta‘kidlaydi.

This article analyses the molecular genetic mechanisms underlying the development of salivary gland tumours. The main genetic mutations (PLAG1, HMGA2, CTNNB1) and their influence on tumour growth are considered. The role of the signal transduction pathways disrupted in the process of carcinogenesis (Wnt/β-catenin, PI3K/AKT/mTOR, NF-kB) is described. Particular attention is paid to the expression of molecular markers (CK7, p40, p63, SOX10, S-100) and to their diagnostic significance. The influence of chronic inflammation and of proinflammatory cytokines (IL-6, TNF-α) on tumour development is discussed. This review article emphasises the need to identify molecular targets for the treatment of salivary gland tumours and to develop new diagnostic and therapeutic strategies.

В статье анализируются молекулярно-генетические механизмы, лежащие в основе развития опухолей слюнных желез. Рассматриваются ключевые генетические мутации (PLAG1, HMGA2, CTNNB1) и их влияние на рост опухолей. Подчеркнута роль нарушенных сигнальных путей (Wnt/β-катенин, PI3K/AKT/mTOR, NF- κB) в канцерогенезе. Особое внимание уделено экспрессии молекулярных маркеров (CK7, p40, p63, SOX10, S-100) и их диагностической значимости. Обсуждается влияние / хронического воспаления и провоспалительных цитокинов (ИЛ-6, ФНО-α) на развитие опухолей. В данной обзорной статье подчеркивается необходимость выявления молекулярных мишеней и разработки новых диагностических и терапевтических стратегий лечения опухолей слюнных желез.

 so‘lak bezlari o‘smalari molekulyar-genetik mexanizmlar PLAG1 HMGA2 CTNNB1 signal uzatish yo‘llari Wnt/β-katenin PI3K/AKT/mTOR NF-kB molekulyar belgilar CK7 p40 p63 SOX10 S-100 yallig‘lanish IL-6 TNF-α so‘lak bezlari o‘smalari molekulyar-genetik mexanizmlar PLAG1 HMGA2 CTNNB1 signal uzatish yo‘llari Wnt/β-katenin PI3K/AKT/mTOR NF-kB molekulyar belgilar CK7 p40 p63 SOX10 S-100 yallig‘lanish IL-6 TNF-α. опухоли слюнных желез молекулярно-генетические механизмы PLAG1 HMGA2 CTNNB1 сигнальные пути Wnt/β-катенин PI3K/AKT/mTOR NF-κB молекулярные маркеры CK7 p40 p63 SOX10 S-100 воспаление IL-6 TNF-α Santos D, Rodrigues-Fernandes ES, Speight CI, Khurram PM, Alsanie SA, Normando I, et al. Impact of tumor site on the prognosis of salivary gland neoplasms: A systematic review and metaanalysis. Critical reviews in oncology/hematology. 2021;162. Egal ESA, Scarini JF, de Lima-Souza RA, Lavareze L, Fernandes PM, Emerick C, et al. Tumor microenvironment in salivary gland carcinomas: An orchestrated state of chaos. Oral Oncol [Internet]. 2022;127(105777):105777. Available from: http://dx.doi.org/10.1016/j.oraloncology.2022.105777 Skálová A, Hyrcza MD, Leivo I. Update from the 5th edition of the World Health Organization Classification of Head and neck tumors: Salivary glands. Head Neck Pathol [Internet]. 2022;16(1):40– 53. Available from: http://dx.doi.org/10.1007/s12105-022-01420-1 Żurek M, Fus Ł, Niemczyk K, Rzepakowska A. Salivary gland pathologies: evolution in classification and association with unique genetic alterations. Eur Arch Otorhinolaryngol [Internet]. 2023;280(11):4739–50. Available from: http://dx.doi.org/10.1007/s00405-023-08110-w Shi Z-D, Pang K, Wu Z-X, Dong Y, Hao L, Qin J-X, et al. Tumor cell plasticity in targeted therapy- induced resistance: mechanisms and new strategies. Signal Transduct Target Ther [Internet]. 2023;8(1):113. Available from: http://dx.doi.org/10.1038/s41392-023-01383-x Toper MH, Sarioglu S. Molecular pathology of salivary gland neoplasms: Diagnostic, prognostic, and predictive perspective: Diagnostic, prognostic, and predictive perspective. Adv Anat Pathol [Internet]. 2021;28(2):81–93. Available from: http://dx.doi.org/10.1097/PAP.0000000000000291 Naik U, Amin SE, Elsayad M, Saluja K. Pleomorphic Adenoma with a Novel Gene Rearrangement- LINC01606:: PLAG1. Head and Neck Pathology. 2024;18. Owosho AA, Adesina OM, Odujoko O, Akinyemi H, Komolafe A, Tadros S, et al. HMGA2 Immunoexpression is frequent in salivary gland pleomorphic adenoma: immunohistochemical and molecular analyses of PLAG1 and HMGA2 in 25 cases. Int J Clin Exp Pathol. 2022;15(2):63–71. Broseghini E, Carosi F, Berti M, Compagno S, Ghelardini A, Fermi M, et al. Salivary gland cancers in the era of molecular analysis: The role of tissue and liquid biomarkers. Cancers (Basel) [Internet]. 2025;17(4). Available from: http://dx.doi.org/10.3390/cancers17040660 Swid MA, Li L, Drahnak EM, Idom H, Quinones W. Updated salivary gland immunohistochemistry: A review. Arch Pathol Lab Med [Internet]. 2023;147(12):1383–9. Available from: http://dx.doi. org/10.5858/arpa.2022-0461-RA Pikul J, Rzepakowska A. Molecular landscape of salivary gland malignancies. What is already known? Contemp Oncol (Pozn) [Internet]. 2024;28(3):201–16. Available from: http://dx.doi. org/10.5114/wo.2024.144288 Song P, Gao Z, Bao Y, Chen L, Huang Y, Liu Y, et al. Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J Hematol Oncol [Internet]. 2024;17(1):46. Available from: http:// dx.doi.org/10.1186/s13045-024-01563-4 Stefani C, Miricescu D, Stanescu-Spinu I-I, Nica RI, Greabu M, Totan AR, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: Where are we now? Int J Mol Sci [Internet]. 2021;22(19):10260. Available from: http://dx.doi.org/10.3390/ ijms221910260 Moneva-Sakelarieva M, Kobakova Y, Konstantinov S, Momekov G, Ivanova S, Atanasova V, et al. The role of the transcription factor NF-kB in the pathogenesis of inflammation and carcinogenesis. Modulation capabilities. Pharmacia. 2025;72:1–13. He K, Gan WJ. Wnt/β-catenin signaling pathway in the development and progression of colorectal cancer. Cancer Management and Research. 2023;435–48. Ouedraogo SY, Zoure AA, Zeye MMJ, Kiendrebeogo TI, Zhou X, Sawadogo AY, et al. BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 genes mutations in Burkina Faso breast cancer patients: prevalence, spectrum and novel variant. Mol Genet Genomics [Internet]. 2022;297(5):1257–68. Available from: http://dx.doi.org/10.1007/s00438-022-01914-1 Panwar V, Singh A, Bhatt M, Tonk RK, Azizov S, Raza AS, et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct Target Ther [Internet]. 2023;8(1):375. Available from: http://dx.doi.org/10.1038/s41392-023- 01608-z 10.1038/s41392-023-01608-z De Mello Gomes ÁN, Oliveira KK, Marchi FA, Bettim BB, Germano JN, Gonçalves Filho J, et al. TGFβ signaling pathway in salivary gland tumors. Archives of Oral Biology. 2024;162. Basset CA, Hajj Hussein I, Jurjus AR, Cappello F, Conway de Macario E, Macario AJL, et al. The chaperone Hsp90, a key player in salivary gland tumorigenesis. Applied Biosciences [Internet]. 2023;2(4):607–16. Available from: http://dx.doi.org/10.3390/applbiosci2040038 Nonaka T, Takei H. Immunohistochemical profile of polymorphous adenocarcinoma of minor salivary gland: A systematic review and meta-analysis. Head Neck Pathol [Internet]. 2022;16(4):980– 90. Available from: http://dx.doi.org/10.1007/s12105-022-01453-6 Ruddle NH. Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer. Current Opinion in Physiology. 2023;36. Sivakumar N, Narwal A, Pandiar D, Devi A, Anand R, Bansal D, et al. Diagnostic utility of p63/ p40 in the histologic differentiation of salivary gland tumors: a systematic review. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2022;133:189–98. Steurer S, Riemann C, Büscheck F, Luebke AM, Kluth M, Hube-Magg C, et al. P63 expression in human tumors and normal tissues: A tissue microarray study on 10,200 tumors. Biomark Res [Internet]. 2021;9(1):7. Available from: http://dx.doi.org/10.1186/s40364-021-00260-5 Gonzalez MF, Husain BH. Solitary fibrous tumour of the submandibular gland: Novel insights from clinical practice on a close mimicker of pleomorphic adenoma and a diagnostic challenge for the cytopathologist. Cytopathology [Internet]. 2021;32(2):261–5. Available from: http://dx.doi.org/10.1111/ cyt.1293 Steurer S, Riemann C, Büscheck F, Luebke AM, Kluth M, Hube-Magg C, et al. P63 expression in human tumors and normal tissues: A tissue microarray study on 10,200 tumors. Biomark Res [Internet]. 2021;9(1):7. Available from: http://dx.doi.org/10.1186/s40364-021-00260-5 Gonzalez MF, Husain BH. Solitary fibrous tumour of the submandibular gland: Novel insights from clinical practice on a close mimicker of pleomorphic adenoma and a diagnostic challenge for the cytopathologist. Cytopathology [Internet]. 2021;32(2):261–5. Available from: http://dx.doi.org/10.1111/ cyt.1293