Tryambak Pratap Srivastava, Swati Ajmeriya, Isha Goel, Joyeeta Talukdar, Anurag Srivastava, Rajinder Parshad, S V S Deo, Sandeep R Mathur, Ajay Gogia, Avdhesh Rai, Ruby Dhar, Subhradip Karmakar
{"title":"雄激素受体剪接变体 7 (AR-V7) 在乳腺癌发病机制中的预后作用。","authors":"Tryambak Pratap Srivastava, Swati Ajmeriya, Isha Goel, Joyeeta Talukdar, Anurag Srivastava, Rajinder Parshad, S V S Deo, Sandeep R Mathur, Ajay Gogia, Avdhesh Rai, Ruby Dhar, Subhradip Karmakar","doi":"10.1186/s12885-024-13165-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis.</p><p><strong>Methods: </strong>In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes.</p><p><strong>Results: </strong>AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists' treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression.</p><p><strong>Conclusions: </strong>Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1398"},"PeriodicalIF":3.4000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562864/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prognostic role of Androgen Receptor splice variant 7 (AR-V7) in the pathogenesis of breast cancer.\",\"authors\":\"Tryambak Pratap Srivastava, Swati Ajmeriya, Isha Goel, Joyeeta Talukdar, Anurag Srivastava, Rajinder Parshad, S V S Deo, Sandeep R Mathur, Ajay Gogia, Avdhesh Rai, Ruby Dhar, Subhradip Karmakar\",\"doi\":\"10.1186/s12885-024-13165-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis.</p><p><strong>Methods: </strong>In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes.</p><p><strong>Results: </strong>AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists' treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression.</p><p><strong>Conclusions: </strong>Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.</p>\",\"PeriodicalId\":9131,\"journal\":{\"name\":\"BMC Cancer\",\"volume\":\"24 1\",\"pages\":\"1398\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562864/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12885-024-13165-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12885-024-13165-x","RegionNum":2,"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
摘要
背景：雄激素受体（AR）已成为乳腺癌的内分泌治疗靶点，在临床病例中的表达率高达80%。AR-V7是AR的一种组成性激活剪接变体，具有截短的配体结合结构域（LBD），具有配体依赖性转录活性，对比卡鲁胺或恩杂鲁胺等以LBD为靶点的非甾体抗雄激素具有抗药性。在转移性前列腺癌中，AR-V7 水平的升高会导致耐药性和转移的增加：在这项研究中，我们评估了细胞系中 AR 和 AR-V7 的表达情况，并对 89 名接受手术治疗的未接受过治疗的乳腺癌患者进行了队列分析。我们还进一步进行了临床病理相关性分析和生存分析，以评估 AR 和 AR-V7 表达与临床结果之间的关系：结果：TNBC细胞系中AR-V7/AR-FL比率升高，AR拮抗剂治疗后AR-FL下调导致AR-V7代偿性升高。临床样本显示，与对照病例相比，肿瘤中 AR 和 AR-V7 的表达明显升高。进一步的临床病理相关性显示，侵袭性临床特征、较高的病理分级和较差的生存率与AR-V7的表达有关：我们的研究揭示了AR-V7是不良临床结局的标志物，可预测乳腺癌的侵袭性，并鼓励将AR-V7视为可能的治疗干预靶点。
Prognostic role of Androgen Receptor splice variant 7 (AR-V7) in the pathogenesis of breast cancer.
Background: The Androgen Receptor (AR) has emerged as an endocrine therapy target in Breast Cancer, exhibiting up to 80% expression in clinical cases. AR-V7, a constitutively activated splice variant of AR with a truncated ligand-binding domain (LBD), demonstrates ligand-independent transcriptional activity and resistance to nonsteroidal antiandrogens like Bicalutamide or Enzalutamide, targeting the LBD. In metastatic prostate cancer, elevated AR-V7 levels lead to therapeutic resistance and increased metastasis.
Methods: In this study, we evaluated the expression of AR and AR-V7 in cell lines and a cohort of 89 patients undergoing surgical intervention for treatment-naïve breast cancer. Further clinicopathological correlations and survival analysis were performed to evaluate the relationship between the AR and AR-V7 expression and clinical outcomes.
Results: AR-V7/AR-FL ratio was elevated in the TNBC cell line and downregulation of AR-FL upon AR antagonists' treatment led to a compensatory increase in AR-V7. Clinical samples showed significantly elevated expression of AR and AR-V7 in tumors compared to control cases. Further clinicopathological correlation revealed aggressive clinical traits, higher pathological grades, and poor survival with AR-V7 expression.
Conclusions: Our study unravels AR-V7 as a marker for poor clinical outcomes, predicting breast cancer aggressiveness, and encourages consideration of AR-V7 as a probable target for therapeutic intervention.
期刊介绍：
BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
