Yazan R Alhamdan, Nehad M Ayoub, Sara K Jaradat, Aymen Shatnawi, Rami J Yaghan
{"title":"BRAF 表达和拷贝数改变可预测乳腺癌患者的不利肿瘤特征和不良预后。","authors":"Yazan R Alhamdan, Nehad M Ayoub, Sara K Jaradat, Aymen Shatnawi, Rami J Yaghan","doi":"10.1155/2024/6373900","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. <b>Methods:</b> The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral <i>BRAF</i> mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of <i>BRAF</i> expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of <i>BRAF</i> mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. <b>Results:</b> BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (<i>p</i> < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (<i>p</i> = 0.003). The average <i>BRAF</i> mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. <i>BRAF</i> gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high <i>BRAF</i> mRNA expression. <b>Conclusion:</b> High <i>BRAF</i> mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.</p>","PeriodicalId":46159,"journal":{"name":"International Journal of Breast Cancer","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199069/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>BRAF</i> Expression and Copy Number Alterations Predict Unfavorable Tumor Features and Adverse Outcomes in Patients With Breast Cancer.\",\"authors\":\"Yazan R Alhamdan, Nehad M Ayoub, Sara K Jaradat, Aymen Shatnawi, Rami J Yaghan\",\"doi\":\"10.1155/2024/6373900\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. <b>Methods:</b> The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral <i>BRAF</i> mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of <i>BRAF</i> expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of <i>BRAF</i> mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. <b>Results:</b> BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (<i>p</i> < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (<i>p</i> = 0.003). The average <i>BRAF</i> mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. <i>BRAF</i> gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high <i>BRAF</i> mRNA expression. <b>Conclusion:</b> High <i>BRAF</i> mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.</p>\",\"PeriodicalId\":46159,\"journal\":{\"name\":\"International Journal of Breast Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-05-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199069/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Breast Cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2024/6373900\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Breast Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2024/6373900","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
BRAF Expression and Copy Number Alterations Predict Unfavorable Tumor Features and Adverse Outcomes in Patients With Breast Cancer.
Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. BRAF gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.
期刊介绍:
International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.