TY - BOOK AU - Amira Hossny Awad Hassan Elbanna, AU - Sherif Abdelaziz Ibrahim AU - Ahmed Hassan Abd El-Raouf AU - Mahmoud Mohamed Kamel TI - Expression pattern and clinical significance of EXT1 in breast cancer U1 - 616.99449 PY - 2025/// KW - Breast cancer KW - سرطان الثدى KW - Exostosin 1 (EXT1) KW - Heparan Sulfate KW - breast cancer KW - prognosis KW - immune infiltration N1 - Thesis (M.Sc)-Cairo University, 2025; Bibliography: pages 75-96; Issues also as CD N2 - Background: Exostosin 1 (EXT1) encodes a type II transmembrane glycosyltransferase residing in the endoplasmic reticulum and plays an essential role in the elongation of heparan sulfate chain biosynthesis. Additionally, EXT1 may act as an oncogene, promoting cell proliferation and metastasis of cancer cells. Aim of study: to assess the expression pattern, prognostic value, and immunological implications of EXT1 in breast cancer. Materials and Methods: Immunohistochemical staining of EXT1 was evaluated in 85 breast cancer patients. Patients were categorized into molecular subtypes, such as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and triple-negative breast cancer (TNBC). Correlations of EXT1 immunostaining with clinicopathological parameters, tumor immune infiltration, and immune cell surface markers assessed by TIMER were analyzed. Furthermore, survival analysis was conducted to reveal EXT1’s prognostic value. Results: EXT1 expression was significantly associated with estrogen receptor (ER) status, molecular sub-types, and recurrence status. Moreover, EXT1 expression was positively associated with poor overall survival (OS) and relapse-free survival (RFS). Immune infiltration analysis indicated that EXT1 expression was positively correlated with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs), although it showed a negative correlation with tumor purity. Conclusion: Overall, this study suggests that the elevated EXT1 expression, particularly in TNBC, is positively correlated with poor prognosis and with immune-infiltrated cells in breast cancer. Therefore, it may emerge as an independent prognostic biomarker, immunological marker, and a potential future therapeutic target for the most aggressive TNBC subtype; اﻟﺨﻠﻔﯿﺔ: ﯾُﺸﻔّﺮ ﺟﯿﻦ اﻛﺴﻮﺳﺘﻮﺳﻦ 1) EXT1) ﻹﻧﺰﯾﻢ ﻏﻠﯿﻜﻮزﯾﻠﺘﺮاﻧﺴﻔﯿﺮاز ﻣﻦ اﻟﻨﻮع اﻟﺜﺎﻧﻲ اﻟﺬي ﯾﻘﺒﻊ ﻓﻲ اﻟﺸﺒﻜﺔ اﻹﻧﺪوﺑﻼزﻣﯿﺔ، وﯾﻠﻌﺐ دورً ا أﺳﺎﺳﯿًﺎ ﻓﻲ إطﺎﻟﺔ ﺳﻠﺴﻠﺔ ﺗﺨﻠﯿﻖ اﻟﮭﯿﺒﺎران ﺳﻠﻔﺎت. ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ذﻟﻚ، ﻗﺪ ﯾﻌﻤﻞEXT1 ﻛﺠﯿﻦ ﻣﺴﺮطﻦ، ﻣﻤﺎ ﯾﻌﺰز ﺗﻜﺎﺛﺮ اﻟﺨﻼﯾﺎ واﻧﺘﻘﺎل اﻟﺨﻼﯾﺎ اﻟﺴﺮطﺎﻧﯿﺔ. ھﺪف اﻟﺪراﺳﺔ :ﻛﺎن اﻟﮭﺪف ﻣﻦ اﻟﺪراﺳﺔ ﺗﻘﯿﯿﻢ ﻧﻤﻂ اﻟﺘﻌﺒﯿﺮ واﻟﻘﯿﻤﺔ اﻟﺘﻨﺒﺆﯾﺔ واﻵﺛﺎر اﻟﻤﻨﺎﻋﯿﺔ ﻟـEXT1 ﻓﻲ ﺳﺮطﺎن اﻟﺜﺪي. اﻟﻤﻮاد واﻟﻄُﺮق :ﺗﻢ ﺗﻘﯿﯿﻢ ﺻﺒﻐﺔ اﻟﻤﻨﺎﻋﯿﺔ ﻟـEXT1 ﻓﻲ 85 ﻣﺮﯾﻀﺔ ﺑﺴﺮطﺎن اﻟﺜﺪي. ﺗﻢ ﺗﺼﻨﯿﻒ اﻟﻤﺮﺿﻰ إﻟﻰ اﻷﻧﻮاع اﻟﻔﺮﻋﯿﺔ اﻟﺠﺰﯾﺌﯿﺔ ﻣﺜﻞ ﻟﻮﻣﻨﺎلA ، ﻟﻮﻣﻨﺎلB ، ﻣﺴﺘﻘﺒﻼت ﻋﺎﻣﻞ اﻟﻨﻤﻮ اﻟﺒﺸﺮي HER2)2) ، وﺳﺮطﺎن اﻟﺜﺪي اﻟﺜﻼﺛﻲ اﻟﺴﻠﺒﻲ TNBC)(. ﺗﻢ ﺗﺤﻠﯿﻞ اﻟﻌﻼﻗﺎت ﺑﯿﻦ ﺻﺒﻐﺔ EXT1اﻟﻤﻨﺎﻋﯿﺔ واﻟﻤﻌﺎﯾﯿﺮ اﻹﻛﻠﯿﻨﯿﻜﯿﺔ اﻟﻤﺮﺿﯿﺔ، ﺗﺴﻠﻞ اﻟﻮرم اﻟﻤﻨﺎﻋﻲ، وﻋﻼﻣﺎت ﺳﻄﺢ اﻟﺨﻼﯾﺎ اﻟﻤﻨﺎﻋﯿﺔ اﻟﺘﻲ ﺗﻢ ﺗﻘﯿﯿﻤﮭﺎ ﺑﺎﺳﺘﺨﺪام ﻗﺎﻋﺪة ﺑﯿﺎﻧﺎت TIMER. ﻋﻼوة ﻋﻠﻰ ذﻟﻚ، ﺗﻢ إﺟﺮاء ﺗﺤﻠﯿﻞ ﻟﻠﺒﻘﺎء ﻟﻠﻜﺸﻒ ﻋﻦ اﻟﻘﯿﻤﺔ اﻟﺘﻨﺒﺆﯾﺔ ﻟـEXT1 . اﻟﻨﺘﺎﺋﺞ :ﻛﺎن ﺗﻌﺒﯿﺮ EXT1 ﻣﺮﺗﺒﻄًﺎ ﺑﺸﻜﻞ ﻛﺒﯿﺮ ﺑﺤﺎﻟﺔ ﻣﺴﺘﻘﺒﻼت اﻹﺳﺘﺮوﺟﯿﻦ ER)(، اﻷﻧﻮاع اﻟﻔﺮﻋﯿﺔ اﻟﺠﺰﯾﺌﯿﺔ، وﺣﺎﻟﺔ اﻟﺘﻜﺮار. ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ذﻟﻚ، ﻛﺎن ﺗﻌﺒﯿﺮEXT1 ﻣﺮﺗﺒﻄًﺎ ﺑﺸﻜﻞ إﯾﺠﺎﺑﻲ ﺑﺴﻮء اﻟﺒﻘﺎء اﻟﻌﺎم OS)( واﻟﺒﻘﺎء اﻟﺨﺎﻟﻲ ﻣﻦ اﻻﻧﺘﻜﺎس RFS)(. أظﮭﺮ ﺗﺤﻠﯿﻞ ﺗﺴﻠﻞ اﻟﻤﻨﺎﻋﺔ أن ﺗﻌﺒﯿﺮ EXT1 ﻛﺎن ﻣﺮﺗﺒﻄًﺎ إﯾﺠﺎﺑﯿًﺎ ﻣﻊ ﺧﻼﯾﺎT اﻟﺴﺎﻣﺔCD8)+( ، ﺧﻼﯾﺎT اﻟﻤﺴﺎﻋﺪة( CD4)+ ، اﻟﺒﻼﻋﻢ، اﻟﺨﻼﯾﺎ اﻟﻤﺘﻌﺎدﻟﺔ، واﻟﺨﻼﯾﺎ اﻟﻤﺘﻐﺼﻨﺔ(DCs) ، ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ أﻧﮫ أظﮭﺮ ارﺗﺒﺎطًﺎ ﺳﻠﺒﯿًﺎ ﻣﻊ ﻧﻘﺎء اﻟﻮرم. اﻟﺨﻼﺻﺔ: ﺑﺸﻜﻞ ﻋﺎم، ﺗﺸﯿﺮ ھﺬه اﻟﺪراﺳﺔ إﻟﻰ أن ارﺗﻔﺎع ﺗﻌﺒﯿﺮEXT1 ، ﺧﺎﺻﺔ ﻓﻲ ﻧﻮعTNBC ، ﻣﺮﺗﺒﻂ ﺑﺸﻜﻞ إﯾﺠﺎﺑﻲ ﺑﺴﻮء اﻟﺘﻨﺒﺆ وﺑﺘﺴﻠﻞ اﻟﺨﻼﯾﺎ اﻟﻤﻨﺎﻋﯿﺔ ﻓﻲ ﺳﺮطﺎن اﻟﺜﺪي. وﺑﺎﻟﺘﺎﻟﻲ، ﻗﺪ ﯾﻈﮭﺮEXT1 ﻛﻌﻼﻣﺔ ﺗﻨﺒﺆﯾﺔ ﻣﺴﺘﻘﻠﺔ، وﻋﻼﻣﺔ ﻣﻨﺎﻋﯿﺔ، وھﺪﻓًﺎ ﻋﻼﺟﯿًﺎ ﻣﺴﺘﻘﺒﻠﯿًﺎ ﻷﻧﻮاع ﺳﺮطﺎن اﻟﺜﺪي اﻷﻛﺜﺮ ﻋﺪواﻧﯿﺔ ER -