DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Autor: Sigin VO; Research Centre for Medical Genetics, 115522 Moscow, Russia., Kalinkin AI; Research Centre for Medical Genetics, 115522 Moscow, Russia., Nikolaeva AF; Research Centre for Medical Genetics, 115522 Moscow, Russia., Ignatova EO; Research Centre for Medical Genetics, 115522 Moscow, Russia.; N. N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia., Kuznetsova EB; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Laboratory of Medical Genetics, I. M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia., Chesnokova GG; Research Centre for Medical Genetics, 115522 Moscow, Russia., Litviakov NV; Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia., Tsyganov MM; Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia., Ibragimova MK; Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia., Vinogradov II; Regional Clinical Oncology Dispensary, 390011 Ryazan, Russia.; Department of Pathological Anatomy, Ryazan State Medical University, 390026 Ryazan, Russia., Vinogradov MI; Regional Clinical Oncology Dispensary, 390011 Ryazan, Russia., Vinogradov IY; Department of Pathological Anatomy, Ryazan State Medical University, 390026 Ryazan, Russia., Zaletaev DV; Research Centre for Medical Genetics, 115522 Moscow, Russia., Nemtsova MV; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Laboratory of Medical Genetics, I. M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia., Kutsev SI; Research Centre for Medical Genetics, 115522 Moscow, Russia., Tanas AS; Research Centre for Medical Genetics, 115522 Moscow, Russia., Strelnikov VV; Research Centre for Medical Genetics, 115522 Moscow, Russia.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Mar 06; Vol. 15 (5). Date of Electronic Publication: 2023 Mar 06.
DOI: 10.3390/cancers15051630
Abstrakt: Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials. An obvious fact is the lack of biomarkers predicting the therapeutic effect of NACT. In a search for epigenetic markers, we performed genome-wide differential methylation screening by XmaI-RRBS in cohorts of NACT responders and nonresponders, for triple-negative (TN) and luminal B tumors. The predictive potential of the most discriminative loci was further assessed in independent cohorts by methylation-sensitive restriction enzyme quantitative PCR (MSRE-qPCR), a promising method for the implementation of DNA methylation markers in diagnostic laboratories. The selected most informative individual markers were combined into panels demonstrating cvAUC = 0.83 ( TMEM132D and MYO15B markers panel) for TN tumors and cvAUC = 0.76 ( TTC34 , LTBR and CLEC14A ) for luminal B tumors. The combination of methylation markers with clinical features that correlate with NACT effect (clinical stage for TN and lymph node status for luminal B tumors) produces better classifiers, with cvAUC = 0.87 for TN tumors and cvAUC = 0.83 for luminal B tumors. Thus, clinical characteristics predictive of NACT response are independently additive to the epigenetic classifier and in combination improve prediction.
Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Databáze: MEDLINE
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