ArticleGenome medicine2024
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy.
Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Artificial intelligence integrated multi-omics and multimodal studies promote the efficacy of neoadjuvant chemotherapy in breast cancer: opportunities, challenges, and future perspectives.Breast cancer research : BCR · 2026Review
- Revealing the Potential Associations of Mutation-Related Genes with Lymph Node Metastasis in Gallbladder Cancer Through Transcriptome and Exome Sequencing.Biomedicines · 2026Article
- Toward genomic personalization of breast cancer radiotherapy: foundations, challenges, and a roadmap for clinical integration.Breast (Edinburgh, Scotland) · 2026Review
- Impact of Clonal Hematopoiesis of Indeterminate Potential on Treatment Response and Tumor Microenvironment in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.Journal of mammary gland biology and neoplasia · 2026Article
- Genomic analysis of radiosensitivity in breast cancer : Identifying pathological determinants and assessing genomic-adjusted radiation dose (GARD) for personalized dose escalation.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Divergent transcriptional programs and constrained metabolic states reveal selective metabolic dependencies in chemoresistant luminal breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- A pretreatment 15-gene signature predicts non-pCR in response to neoadjuvant chemotherapy in breast cancer and reveals a pyruvate-Frontiers in oncology · 2026Article
- Delta-like ligand 4 mediated myeloid-derived suppressor cell metabolic reprogramming promotes neoadjuvant therapy resistance in titin-inactivated triple-negative breast cancer.Molecular biomedicine · 2025Article
- Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.Journal of experimental & clinical cancer research : CR · 2025Review
- Anti-Neoplastic Activity of Estrogen Receptor Beta in Chemoresistant Triple-Negative Breast Cancer.Cancers · 2025Article
- Multi‑omics analysis identifies different molecular subtypes with unique outcomes in early-stage poorly differentiated lung adenocarcinoma.Molecular cancer · 2025Article
- Single-cell omics technologies - Fundamentals on how to create single-cell looking glasses for reproductive health.American journal of obstetrics and gynecology · 2025Review
- The complex interplay between psoriasis and depression: from molecular mechanisms to holistic treatment approaches.Frontiers in immunology · 2025Review
- From trash to treasure: tumor draining lymph nodes as a multi-omics goldmine in cancer therapy.Frontiers in oncology · 2025Review
- Interpretable Machine Learning Algorithms Identify Inetetamab-Mediated Metabolic Signatures and Biomarkers in Treating Breast Cancer.Journal of clinical laboratory analysis · 2024Article
- Whole-exome profiles of inflammatory breast cancer and pathological response to neoadjuvant chemotherapy.Journal of translational medicine · 2024Article
- Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
Corrections and comments
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Authors and funding
28 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNeoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity.
methodsWe performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments.
resultsThe most frequently altered genes were TP53, TTN, and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors (P = 0.020). NAC significantly decreased the mutation rate (P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3) and a deleted region at 3p13 (harboring FOXP1) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients.
conclusionsOur study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers (CDKAL1
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