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Purpose <p>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> Methods <p>The expression of the long non-coding RNA <i>FAM83H-AS1</i> 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 <i>FAM83H-AS1</i> expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed.</p> Results <p>A positive correlation was observed between tumor grade and the expression of <i>FAM83H-AS1, N-cadherin, E-cadherin, and vimentin</i>, whereas <i>FGF-18</i>, <i>TGF-β</i>, and <i>β-catenin</i> were downregulated. Estrogen receptor positivity was associated with <i>CLDN1</i> and <i>Snail-1</i> expression, while <i>HER2</i> positivity was linked to vimentin expression. <i>Snail-1</i> expression correlated positively with <i>Ki-67</i> levels. All genes except <i>MMP2</i> were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in <i>FGF-18</i>, <i>TGF-β</i>, <i>N-cadherin</i>, <i>β-catenin</i>, and <i>MMP2</i> expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. <i>FAM83H-AS1</i> was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of <i>TGF-β, N-cadherin</i>, and <i>β-catenin</i>, suggesting their role in the aggressive nature of this subtype. In contrast, <i>MMP2</i> 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. <i>MMP2</i> and <i>MMP9</i> were significantly upregulated in IBC compared to luminal A.</p> Conclusion <p>&#xa0;<i>FAM83H-AS1</i> 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>

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Molecular Dynamics of Breast Cancer Subtypes: The Role of FAM83H-AS1 Long Non-coding RNA in Breast Cancer Metastasis

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • 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

摘要

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.