Yao Fu | Search PubMed

PubMed2026

Prognostic impact of CEACAM5 in nonsquamous non-small cell lung cancer: a critical reappraisal driven by cut-off optimization.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) has emerged as a promising therapeutic target for antibody-drug conjugates (ADCs) in nonsquamous non-small cell lung cancer (NSCLC). However, the landscape of CEACAM5 protein expression and its association with clinicopathological features in nonsquamous NSCLC remain poorly characterized. This study represents the first comprehensive investigation to profile CEACAM5 protein expression in this specific population using a clinical-grade immunohistochemistry (IHC) assay. METHODS: We retrospectively analyzed 218 patients with resected nonsquamous NSCLC. A standardized IHC assay derived from a clinical trial was employed, utilizing a proprietary monoclonal antibody (clone 769) specifically developed for clinical application. We systematically evaluated the relationship between CEACAM5 expression and tumor characteristics using both a conventional therapeutic threshold (≥50%) and a sensitive data-driven cut-off (>0%) to explore the full spectrum of antigen expression. RESULTS: The assay demonstrated excellent reproducibility. We found that CEACAM5 expression was significantly associated with markers of tumor aggressiveness, including lymphovascular and pleural invasion. Notably, the sensitive >0% cut-off revealed broader biological correlations than the restrictive ≥50% threshold. While CEACAM5 was not an independent prognostic factor in the overall cohort, a stage-specific, hypothesis-generating analysis-supported by external genomic validation-suggested that positive CEACAM5 expression may be associated with a trend towards poorer disease-free survival specifically in early-stage (stage I-II) patients, although this did not reach statistical significance (P=0.06). CONCLUSIONS: This study provides the first detailed characterization of CEACAM5 protein expression in nonsquamous NSCLC, establishing it as a biomarker linked to aggressive disease phenotypes. Our findings suggest that adopting a sensitive detection threshold (>0%) may better capture the population of patients with biologically active CEACAM5, thereby potentially refining candidate selection for targeted therapies and risk stratification in early-stage disease, a hypothesis that warrants prospective validation.

Carcinoembryonic antigen-related cell adhesion mol↗

PubMed2025

Defining three dimensional chromatin structures of pediatric and adolescent B cells using primary B cell and EBV-immortalized B cell reference genomes.

BACKGROUND/PURPOSE: Knowledge of the 3D genome is essential to elucidate genetic mechanisms driving autoimmune diseases. The 3D genome is distinct for each cell type, and it is uncertain whether cell lines faithfully recapitulate the 3D architecture of primary human cells or whether developmental aspects of the pediatric immune system require use of pediatric samples. We undertook a systematic analysis of B cells and B cell lines to compare 3D genomic features encompassing risk loci for juvenile idiopathic arthritis (JIA), systemic lupus (SLE), and type 1 diabetes (T1D). METHODS: We isolated B cells from four healthy individuals, ages 9-17. HiChIP was performed using a CTCF antibody, and CTCF peaks were called within each sample separately. Peaks observed in all four samples were identified. CTCF loops were called within the pediatric samples using three CTCF peak datasets: 1) self-called CTCF consensus peaks called within the pediatric samples, 2) ENCODE's publicly available GM12878 CTCF ChIP-seq peaks, and 3) ENCODE's primary B cell CTCF ChIP-seq peaks from two adult females. Differential looping was assessed within the pediatric samples and each of the three peak datasets. RESULTS: The number of consensus peaks called in the pediatric samples was similar to that identified in ENCODE's GM12878 and primary B cell datasets. We observed < 1% of loops that demonstrated significantly differential looping between peaks called within the pediatric samples themselves and when called using ENCODE GM12878 peaks. Significant looping differences were even fewer when comparing loops of the pediatric called peaks to those of the ENCODE primary B cell peaks. When querying loops found in juvenile idiopathic arthritis, type 1 diabetes, or systemic lupus erythematosus risk haplotypes, we observed significant differences in only 2.2%, 1.0%, and 1.3% loops, respectively, when comparing peaks called within the pediatric samples and ENCODE GM12878 dataset. The differences were even less apparent when comparing loops called with the pediatric vs ENCODE adult primary B cell peak datasets. CONCLUSION: The 3D chromatin architecture in B cells is similar across pediatric, adult, and EBV-transformed cell lines. This conservation of 3D structure includes regions encompassing autoimmune risk haplotypes. Thus, even for pediatric autoimmune diseases, publicly available adult B cell and cell line datasets may be sufficient for assessing effects exerted in the 3D genomic space.

Humans↗