Purpose An effective biomarker for the diagnosis of breast cancer (BC) and benign breast diseases (BBD) is crucial for improving the prognosis. We investigated whether N6-methyladenosine (m6A) can be a diagnostic biomarker of BC.
Materials and Methods We detected the contents of peripheral blood m6A in 62 patients with BC, 41 patients with BBD, and 41 normal controls (NCs) using the colorimetric method. The relative expression of the m6A regulated genes methyltransferase-like 14 (METTL14) and fat mass and obesity-associated (FTO) was analyzed using quantitative real-time polymerase chain reaction.
Results m6A in peripheral blood RNA was significantly higher in patients with BC than that in patients with BBD (p < 0.001) or the NCs (p < 0.001). m6A was closely associated with the disease stage (from stage 0 to stage I-IV, p=0.003). The receiver operating characteristic curve of m6A contained an area under the curve (AUC) value of 0.887 in BC, which was greater than that of carcinoembryonic antigen (CEA) or carbohydrate antigen 153 (CA153). The combination of m6A, CEA, and CA153 improved the AUC to 0.914. The upregulated and downregulated mRNA expression of METTL14 and FTO, respectively, might contribute to the increase of m6A in patients with BC. m6A combined with METTL14 and FTO improved the AUC to 0.929 with a specificity of 97.4% in the peripheral blood of patients with BC.
Conclusion The peripheral blood RNA of m6A might be a valuable biomarker for the diagnosis of BC.
Citations
Citations to this article as recorded by
Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m<sup>6</sup>A-dependent miR-17-5p maturation-induced ZBTB4 depletion Jingyi Ni, Xiaoyun Lu, Xiangxiang Gao, Conghui Jin, Junfeng Mao Acta Biochimica et Biophysica Sinica.2024; 56(1): 114. CrossRef
Unraveling the cross‐talk between N6‐methyladenosine modification and non‐coding RNAs in breast cancer: Mechanisms and clinical implications Xuan Liu, Xuelong Xie, Chentao Sui, Xuexue Liu, Miao Song, Qing Luo, Ping Zhan, Jia Feng, Jinbo Liu International Journal of Cancer.2024; 154(11): 1877. CrossRef
N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer Chunying Zhang, Jiadi Chen, Jingyi Ren, Xiaoyu Li, Yaqin Zhang, Bihan Huang, Yihan Xu, Luyan Dong, Yingping Cao Cancer Cell International.2024;[Epub] CrossRef
Demethylases in tumors and the tumor microenvironment: Key modifiers of N6-methyladenosine methylation Junchen Guo, Liang Zhao, Meiqi Duan, Zhi Yang, He Zhao, Baiming Liu, Yihan Wang, Liping Deng, Chen Wang, Xiaodi Jiang, Xiaofeng Jiang Biomedicine & Pharmacotherapy.2024; 174: 116479. CrossRef
The interaction between m6A modification and noncoding RNA in tumor microenvironment on cancer progression Liushan Wei, Shun Liu, Zhizhong Xie, Guotao Tang, Xiaoyong Lei, Xiaoyan Yang International Immunopharmacology.2024; 140: 112824. CrossRef
Simultaneous detection of membrane protein and mRNA at single extracellular vesicle level by droplet microfluidics for cancer diagnosis Huixian Lin, Bo Li, Jingyun Guo, Xueying Mai, Haiyang Yu, Weilun Pan, Bodeng Wu, Wei Liu, Mingzhen Zhong, Tong Liao, Ye Zhang, Bo Situ, Xiaohui Yan, Yifan Liu, Chunchen Liu, Lei Zheng Journal of Advanced Research.2024;[Epub] CrossRef
METTL protein family: focusing on the occurrence, progression and treatment of cancer Huhu Zhang, Fulin Sun, Shuyao Jiang, Fanghao Yang, Xiaolei Dong, Guoxiang Liu, Mengjun Wang, Ya Li, Mohan Su, Ziyuan Wen, Chunjuan Yu, Chenkai Fan, Xiaoxia Li, Zhe Zhang, Lina Yang, Bing Li Biomarker Research.2024;[Epub] CrossRef
Multiomics analyses and machine learning of nuclear receptor coactivator 6 reveal its essential role in hepatocellular carcinoma Yinghao Fang, Yuyan Xu, Wei Liao, Tao Ji, Linyuan Yu, Longhai Li, Mingxin Pan, Dinghua Yang Cancer Science.2023; 114(1): 75. CrossRef
Effect of Polyphenols and Zinc Co-Supplementation on the Development of Neoplasms in Rats with Breast Cancer Martyna Jastrzębska, Joanna Giebułtowicz, Andrzej K. Ciechanowicz, Robert Wrzesień, Wojciech Bielecki, Barbara Bobrowska-Korczak Foods.2023; 12(2): 356. CrossRef
Understanding the Epitranscriptome for Avant-Garde Brain Tumour Diagnostics Ágota Tűzesi, Susannah Hallal, Laveniya Satgunaseelan, Michael E. Buckland, Kimberley L. Alexander Cancers.2023; 15(4): 1232. CrossRef
Development of a N6-methyladenosine-directed single quantum dot-based biosensor for sensitive detection of METTL3/14 complex activity in breast cancer tissues Ming-hao Liu, Wan-tong Yu, Ning-ning Zhao, Jian-Ge Qiu, Bing-Hua Jiang, Yan Zhang, Chun-yang Zhang Analytica Chimica Acta.2023; 1279: 341796. CrossRef
Functions, mechanisms, and therapeutic implications of METTL14 in human cancer Qian Guan, Huiran Lin, Lei Miao, Huiqin Guo, Yongping Chen, Zhenjian Zhuo, Jing He Journal of Hematology & Oncology.2022;[Epub] CrossRef
Methyladenosine Modification in RNAs: From Regulatory Roles to Therapeutic Implications in Cancer Xiaolin Qu, Yongqiu Zhang, Xianzheng Sang, Ding Ren, Hong Zhao, Stephen T. C. Wong Cancers.2022; 14(13): 3195. CrossRef
METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification Xi Zhang, Xiaonan Zhang, Tengyue Liu, Zhe Zhang, Chiyuan Piao, Hong Ning Journal of Cellular and Molecular Medicine.2022; 26(22): 5602. CrossRef
Regulatory Role of N6-methyladenosine (m6A) Modification in Osteosarcoma Yujie Zhang, Yanyan Wang, Liwei Ying, Sifeng Tao, Mingmin Shi, Peng Lin, Yangxin Wang, Bin Han Frontiers in Oncology.2021;[Epub] CrossRef
Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives Vilbert Sikorski, Pasi Karjalainen, Daria Blokhina, Kati Oksaharju, Jahangir Khan, Shintaro Katayama, Helena Rajala, Satu Suihko, Suvi Tuohinen, Kari Teittinen, Annu Nummi, Antti Nykänen, Arda Eskin, Christoffer Stark, Fausto Biancari, Jan Kiss, Jarmo Sim International Journal of Molecular Sciences.2021; 22(12): 6630. CrossRef
Regulatory roles of RNA modifications in breast cancer Kanchan Kumari, Paula Groza, Francesca Aguilo NAR Cancer.2021;[Epub] CrossRef
m6A target microRNAs in serum for cancer detection Bo Zhang, Zhenmei Chen, Baorui Tao, Chenhe Yi, Zhifei Lin, Yitong Li, Weiqing Shao, Jing Lin, Jinhong Chen Molecular Cancer.2021;[Epub] CrossRef
Purpose
We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH).
Materials and Methods
A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib.
Results
The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients.
Conclusion
Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.
Citations
Citations to this article as recorded by
Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis Chan-Juan Wang, Lei Cui, Shuang-Shuang Li, Hong-Hao Ma, Dong Wang, Hong-Yun Lian, Yun-Ze Zhao, Li-Ping Zhang, Wei-Jing Li, Qing Zhang, Xiao-Xi Zhao, Ying Yang, Xiao-Tong Huang, Wei Liu, Yi-Zhuo Wang, Wan-Shui Wu, Tian-You Wang, Rui Zhang, Zhi-Gang Li Archives of Pathology & Laboratory Medicine.2025; 149(2): 175. CrossRef
Targeted therapy and immunotherapy for orbital and periorbital tumors: a major review Emmanuel Lee Boniao, Richard C. Allen, Gangadhara Sundar Orbit.2024; 43(5): 656. CrossRef
Treatment of children with refractory/relapse high risk langerhans cell histiocytosis with the combination of cytarabine, vindesine and prednisone Wenqian Wang, Jian Ge, Honghao Ma, Hongyun Lian, Lei Cui, Yunze Zhao, Zhigang Li, Tianyou Wang, Rui Zhang BMC Pediatrics.2024;[Epub] CrossRef
Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study Jiaying Lei, Wenxia Wang, Danna Lin, Chengguang Zhu, Wenguang Jia, Wenjun Weng, Xiaoshan Liu, Yuhan Ma, Zhixuan Wang, Lihua Yang, Xiangling He, Yunyan He, Yang LI Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis Xinshun Ge, Wenxin Ou, Ang Wei, Hongyun Lian, Honghao Ma, Lei Cui, Dong Wang, Liping Zhang, Xiaoman Wang, Lejian He, Rui Zhang, Tianyou Wang BMC Pediatrics.2024;[Epub] CrossRef
Refractory juvenile xanthogranuloma of the mastoid bone responsive to trametinib Isaac Hauk, Ignacio Gonzalez‐Gomes, Deepak Chellapandian, Jonathan Metts, Peter H. Shaw Pediatric Blood & Cancer.2024;[Epub] CrossRef
Advancements in the understanding and management of histiocytic neoplasms Kyung-Nam Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im Blood Research.2024;[Epub] CrossRef
Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium Paul G. Kemps, F. J. Sherida H. Woei-A-Jin, Patrick Schöffski, Thomas Tousseyn, Isabelle Vanden Bempt, Friederike A. G. Meyer-Wentrup, Natasja Dors, Natasha K. A. van Eijkelenburg, Marijn A. Scheijde-Vermeulen, Ingrid M. Jazet, Maarten Limper, Margot Jak, Blood Neoplasia.2024; 1(3): 100023. CrossRef
The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis Zi-Jing Zhao, Hong-Yun Lian, Wei-Jing Li, Qing Zhang, Hong-Hao Ma, Dong Wang, Yun-Ze Zhao, Ting Zhu, Hua-Lin Li, Xiao-Tong Huang, Tian-You Wang, Rui Zhang, Lei Cui, Zhi-Gang Li Jornal de Pediatria.2024;[Epub] CrossRef
Liver transplantation in a child with sclerosing cholangitis due to Langerhans cell histiocytosis: a case report Xue-Lian Wang, Chun-Xiao Fang, Min-Xia Chen, Hua-Mei Yang, Lan-Hui She, Yu Gong, Yi Xu, Wei-Qiang Xiao, Jin-Sheng Tian, Bin Ai, Li Huang, Xu-Fang Li Frontiers in Pediatrics.2024;[Epub] CrossRef
BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease Lokman Cevik, Swati Satturwar, Dan Jones, Joel Mayerson, Steve Oghumu, O. Hans Iwenofu Human Pathology.2024; 154: 105702. CrossRef
Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system Evgeniy F. Khynku, Maria K. Monaenkova, Olga B. Tamrazova, Alexey V. Taganov, Мarina А. Gureeva, Gayane E. Bagramova, Anton V. Molochkov Almanac of Clinical Medicine.2023; 50(7): 428. CrossRef
Lineage switching of the cellular distribution of BRAF
V600E in multisystem Langerhans cell histiocytosis Paul Milne, Simon Bomken, Olga Slater, Ashish Kumar, Adam Nelson, Somak Roy, Jessica Velazquez, Kshitij Mankad, James Nicholson, Dan Yeomanson, Richard Grundy, Ahmed Kamal, Anthony Penn, Jane Pears, Gerard Millen, Bruce Morland, James Hayden, Jason Lam, M Blood Advances.2023; 7(10): 2171. CrossRef
Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors Ashley V. Geerlinks, Oussama Abla Pediatric Drugs.2023; 25(4): 399. CrossRef
Dabrafenib, alone or in combination with trametinib, in BRAF V600–mutated pediatric Langerhans cell histiocytosis James A. Whitlock, Birgit Geoerger, Ira J. Dunkel, Michael Roughton, Jeea Choi, Lisa Osterloh, Mark Russo, Darren Hargrave Blood Advances.2023; 7(15): 3806. CrossRef
Therapiestrategien bei Kindern und Jugendlichen mit Langerhanszell
Histiozytosen Anke Elisabeth Barnbrock, Caroline Hutter, Konrad Bochennek, Milen Minkov, Thomas Lehrnbecher Klinische Pädiatrie.2023; 235(06): 342. CrossRef
Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms Benjamin H. Durham, Oshrat Hershkovitz-Rokah, Omar Abdel-Wahab, Mariko Yabe, Young Rock Chung, Gilad Itchaki, Maayan Ben-Sasson, Vered A. Asher-Guz, David Groshar, Seyram A. Doe-Tetteh, Tina Alano, David B. Solit, Ofer Shpilberg, Eli L. Diamond, Roei D. M Blood Advances.2023; 7(23): 7319. CrossRef
Validation of Liquid Chromatography Coupled with Tandem Mass Spectrometry for the Determination of 12 Tyrosine Kinase Inhibitors (TKIs) and Their Application to Therapeutic Drug Monitoring in Adult and Pediatric Populations Marie Bellouard, Jean Donadieu, Pauline Thiebot, Etienne Giroux Leprieur, Philippe Saiag, Isabelle Etting, Pamela Dugues, Emuri Abe, Jean-Claude Alvarez, Islam-Amine Larabi Pharmaceutics.2023; 16(1): 5. CrossRef
Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease Oussama Abla Hematology.2023; 2023(1): 386. CrossRef
Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement Ja-Feng Yao, Dong Wang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Tian-You Wang, Zhi-Gang Li, Jin Jiang, Lei Cui, Rui Zhang The Journal of Pediatrics.2022; 244: 194. CrossRef
Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis Dong Wang, Xi-Hua Chen, Ang Wei, Chun-Ju Zhou, Xue Zhang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Qing Zhang, Xiao-Tong Huang, Chan-Juan Wang, Ying Yang, Wei Liu, Tian-You Wang, Zhi-Gang Li, Lei Cui, Rui Zhang Orphanet Journal of Rare Diseases.2022;[Epub] CrossRef
Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis: A narrative review Jagadeesh Menon, Ashwin Rammohan, Mukul Vij, Naresh Shanmugam, Mohamed Rela World Journal of Gastroenterology.2022; 28(30): 4044. CrossRef
Research Progress of BRAF V600E Gene Mutation in Papillary Thyroid Carcinoma 延泽 刘 Advances in Clinical Medicine.2022; 12(09): 8499. CrossRef
Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis Jin Kyung Suh, Sunghan Kang, Hyery Kim, Ho Joon Im, Kyung-Nam Koh BLOOD RESEARCH.2021; 56(S1): S65. CrossRef
Improvement in Pituitary Imaging After Targeted Therapy in Three Children with BRAF-Mutated Langerhans Cell Histiocytosis with Pituitary Involvement
Ying Yang, Dong Wang, Na Li, Honghao Ma, Hongyun Lian, Lei Cui, Qing Zhang, Xiaoxi Zhao, Liping Zhang, Yunze Zhao, Chanjuan Wang, Li Zhang, Tianyou Wang, Zhigang Li, Rui Zhang OncoTargets and Therapy.2020; Volume 13: 12357. CrossRef