{"title":"Molecular Dynamics of Breast Cancer Subtypes: The Role of FAM83H-AS1 Long Non-coding RNA in Breast Cancer Metastasis.","authors":"Mohammad Hossein Hashemi, Hassan Moaiery, Bahram Nikkhoo, Fatemeh Zamani, Soma Mahmoodian, Marzieh Soheili, Farzad Soleimani, Zhila Bahramirad, MohammadBagher KhademErfan, Bayazid Ghaderi, Mohammad Erfan Keyhani, Sherko Nasseri","doi":"10.1007/s10549-024-07603-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer is the leading cause of cancer-related deaths in women. Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are emerging as major players in cancer biology, This study investigates the expression of FAM83H-AS1 in breast cancer and its association with tumor grade, hormone receptors, pathological diagnosis, and molecular markers related to epithelial-mesenchymal transition (EMT).</p><p><strong>Methods: </strong>The expression of the long non-coding RNA FAM83H-AS1 in 80 breast cancer patients was assessed using quantitative real-time PCR (qRT-PCR). Clinical significance was evaluated through histopathological and immunohistochemical analyses. The associations of FAM83H-AS1 expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed.</p><p><strong>Results: </strong>A positive correlation was observed between tumor grade and the expression of FAM83H-AS1, N-cadherin, E-cadherin, and vimentin, whereas FGF-18, TGF-β, and β-catenin were downregulated. Estrogen receptor positivity was associated with CLDN1 and Snail-1 expression, while HER2 positivity was linked to vimentin expression. Snail-1 expression correlated positively with Ki-67 levels. All genes except MMP2 were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in FGF-18, TGF-β, N-cadherin, β-catenin, and MMP2 expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. FAM83H-AS1 was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of TGF-β, N-cadherin, and β-catenin, suggesting their role in the aggressive nature of this subtype. In contrast, MMP2 was downregulated in TNBC compared to IBC, potentially indicating a suppressive role in tumor invasion in TNBC. Vimentin was upregulated in IBC compared to luminal A, indicating its involvement in IBC's aggressive behavior. MMP2 and MMP9 were significantly upregulated in IBC compared to luminal A.</p><p><strong>Conclusion: </strong> FAM83H-AS1 shows potential as a prognostic biomarker and therapeutic target, especially in TNBC and IBC, with implications for personalized breast cancer treatment strategies. Its expression correlates with tumor grade, hormone receptor status, and EMT markers, suggesting a role in cancer progression and metastasis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10549-024-07603-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Breast cancer is the leading cause of cancer-related deaths in women. Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are emerging as major players in cancer biology, This study investigates the expression of FAM83H-AS1 in breast cancer and its association with tumor grade, hormone receptors, pathological diagnosis, and molecular markers related to epithelial-mesenchymal transition (EMT).
Methods: The expression of the long non-coding RNA FAM83H-AS1 in 80 breast cancer patients was assessed using quantitative real-time PCR (qRT-PCR). Clinical significance was evaluated through histopathological and immunohistochemical analyses. The associations of FAM83H-AS1 expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed.
Results: A positive correlation was observed between tumor grade and the expression of FAM83H-AS1, N-cadherin, E-cadherin, and vimentin, whereas FGF-18, TGF-β, and β-catenin were downregulated. Estrogen receptor positivity was associated with CLDN1 and Snail-1 expression, while HER2 positivity was linked to vimentin expression. Snail-1 expression correlated positively with Ki-67 levels. All genes except MMP2 were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in FGF-18, TGF-β, N-cadherin, β-catenin, and MMP2 expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. FAM83H-AS1 was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of TGF-β, N-cadherin, and β-catenin, suggesting their role in the aggressive nature of this subtype. In contrast, MMP2 was downregulated in TNBC compared to IBC, potentially indicating a suppressive role in tumor invasion in TNBC. Vimentin was upregulated in IBC compared to luminal A, indicating its involvement in IBC's aggressive behavior. MMP2 and MMP9 were significantly upregulated in IBC compared to luminal A.
Conclusion: FAM83H-AS1 shows potential as a prognostic biomarker and therapeutic target, especially in TNBC and IBC, with implications for personalized breast cancer treatment strategies. Its expression correlates with tumor grade, hormone receptor status, and EMT markers, suggesting a role in cancer progression and metastasis.
期刊介绍：
Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.
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