Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity. Here we show mFISHseq has 93% accuracy compared to immunohistochemistry. Our consensus subtyping and risk groups mitigate single sample discordance, provide early and late prognostic information, and identify high risk patients with enriched immune signatures, which predict response to neoadjuvant immunotherapy in the multicenter, phase II, prospective I-SPY2 trial. We identify putative antibody-drug conjugate (ADC)-responsive patients, as evidenced by a 19-feature T-DM1 classifier, validated on I-SPY2. Deploying mFISHseq as a research-use only test on 48 patients demonstrates clinical feasibility, revealing insights into the efficacy of targeted therapies, like CDK4/6 inhibitors, immunotherapies, and ADCs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41467-024-55583-2 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696812 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.
View Article and Find Full Text PDFUntangling the complex relationship between bipolar disorder and anxiety: a comprehensive review of prevalence, prognosis, and therapy.
J Neural Transm (Vienna)
January 2025
Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, 13 Liulin Road, Tianjin, 300222, China.
Bipolar disorder (BD) frequently coexists with anxiety disorders, creating complex challenges in clinical therapy and management. This study investigates the prevalence, prognostic implications, and treatment strategies for comorbid BD and anxiety disorders. High comorbidity rates, particularly with generalized anxiety disorder, underscore the necessity of thorough clinical assessments to guide effective management.
View Article and Find Full Text PDFCopy Number Variation in Asthma: An Integrative Review.
Clin Rev Allergy Immunol
January 2025
Postgraduate Program in Biochemistry, Federal University of Espírito Santo (UFES), Vitória, Espírito Santo, Brazil.
Asthma is a complex disease with varied clinical manifestations resulting from the interaction between environmental and genetic factors. While chronic airway inflammation and hyperresponsiveness are central features, the etiology of asthma is multifaceted, leading to a diversity of phenotypes and endotypes. Although most research into the genetics of asthma focused on the analysis of single nucleotide polymorphisms (SNPs), studies highlight the importance of structural variations, such as copy number variations (CNVs), in the inheritance of complex characteristics, but their role has not yet been fully elucidated in asthma.
View Article and Find Full Text PDFInflammatory markers predict efficacy of immunotherapy in advanced non-small cell lung cancer: a preliminary exploratory study.
Discov Oncol
January 2025
Department of Respiratory Medicine, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), 1882 South Zhonghuan Road, Jiaxing, 314000, Zhejiang, China.
Objective: The purpose of this study is to analyze the predictive value of neutrophil to lymphocyte ratio (NLR), lymphocyte count to monocyte count ratio (LMR), platelet to lymphocyte ratio (PLR), platelet count multiplied by neutrophil count to lymphocyte count ratio (SII), red blood cell distribution width (RDW), packed cell volume (PCV), and plateletcrit (PCT) levels in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
Materials And Methods: From March 2019 to August 2023, we screened 104 of 153 patients with stage III unresectable local advanced NSCLC and IV NSCLC who received PD-1/PD-L1 inhibitor therapy at our hospital and met the inclusion and exclusion criteria for analysis. All patients were collected for clinical information, including baseline blood indicator (NLR, PLR, LMR, SII, CRP, RDW, PCV and PCT) levels before PD-1/PD-L1 inhibitor therapy and blood indicator levels and imaging evaluation results every two cycles after PD-1/PD-L1 inhibitor therapy.
Lymph-node ratio as a risk factor for recurrence following neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy for locally advanced esophageal squamous cell carcinoma.
Esophagus
January 2025
Department of Gastroenterological Chemotherapy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan.
Background And Purpose: It remains unclear whether the lymph-node ratio (LNR) is a relevant factor for the risk of recurrence following neoadjuvant chemotherapy (nCT) with docetaxel, cisplatin, and 5-fluorouracil (DCF), which is a new standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. This study aimed to evaluate the clinical utility of LNR as a risk factor for recurrence.
Materials And Methods: We retrospectively analyzed 75 patients who underwent nCT-DCF followed by curative surgery for resectable ESCC.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!