Zdrehus Razvan-Septimiu, Mitrea Cristina, Mocan Lucian
Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
Department of Computational Medicine and Bioinformatics, University of Michigan, USA.
Med Pharm Rep. 2025 Jul;98(3):358-370. doi: 10.15386/mpr-2917. Epub 2025 Jul 30.
Carcinoembryonic antigen (CEA/CEACAM5) is a well-established tumor-associated antigen overexpressed in epithelial malignancies, including colorectal cancer (CRC). While its diagnostic and therapeutic relevance is recognized, its immunological context and potential as a nanovaccine target remain underexplored.
This study aims to enable the rational design and refinement of CEA-based nanovaccines by integrating transcriptomic and spatial data to identify immunologically relevant co-expressed biomarkers and potential therapeutic targets.
We conducted an integrative bioinformatics analysis using transcriptomic data from TCGA-COAD, GEO, and spatial datasets (GSE207843, GSE226997), complemented by differential gene expression analysis (GSE245218). CEACAM5 expression was correlated with cytokine profiles (IL10, IFNG, TNF, IL1B, IL12A, IL4), immune cell infiltration (via xCell), and co-expression networks. Genes with Spearman ρ > 0.75 were prioritized as vaccine candidates and evaluated through oncofetal expression and literature curation.
CEACAM5 expression was inversely correlated with IFNG, IL10, TNF, and IL1B, suggesting a potential immunosuppressive phenotype. xCell analysis revealed negative trends between CEACAM5 and effector immune populations including CD8 T cells and NK cells. Spatial transcriptomics confirmed CEACAM5 compartmentalization in tumor epithelium with minimal cytokine overlap. Co-expression analysis identified EPCAM and ATP10B as high-confidence candidates. Embryonic vs. adult differential analysis (GSE245218) confirmed their oncofetal expression patterns. Gene ontology analysis revealed downregulation of antibacterial humoral immune pathways.
CEACAM5 defines a distinct immune-silent tumor phenotype and co-localizes with other vaccine-relevant genes such as EPCAM. This study provides a comprehensive immunogenomic rationale for CEACAM5-directed nanovaccine development and proposes EPCAM and ATP10B as co-targets based on tumor-specific and developmental expression profiles.
癌胚抗原（CEA/CEACAM5）是一种公认的肿瘤相关抗原，在上皮性恶性肿瘤中过表达，包括结直肠癌（CRC）。虽然其诊断和治疗相关性已得到认可，但其免疫背景和作为纳米疫苗靶点的潜力仍未得到充分探索。
本研究旨在通过整合转录组学和空间数据，以识别免疫相关的共表达生物标志物和潜在治疗靶点，从而实现基于CEA的纳米疫苗的合理设计和优化。
我们使用来自TCGA-COAD、GEO的转录组数据和空间数据集（GSE207843、GSE226997）进行了综合生物信息学分析，并辅以差异基因表达分析（GSE245218）。CEACAM5表达与细胞因子谱（IL10、IFNG、TNF、IL1B、IL12A、IL4）、免疫细胞浸润（通过xCell）和共表达网络相关。将Spearman ρ>0.75的基因优先作为疫苗候选基因，并通过胎儿期表达和文献梳理进行评估。
CEACAM5表达与IFNG、IL10、TNF和IL1B呈负相关，提示潜在的免疫抑制表型。xCell分析显示CEACAM5与效应免疫细胞群体（包括CD8 T细胞和NK细胞）之间呈负相关趋势。空间转录组学证实CEACAM5在肿瘤上皮中的分区，细胞因子重叠最少。共表达分析确定EPCAM和ATP10B为高可信度候选基因。胚胎与成人差异分析（GSE245218）证实了它们的胎儿期表达模式。基因本体分析显示抗菌体液免疫途径下调。
CEACAM5定义了一种独特的免疫沉默肿瘤表型，并与其他与疫苗相关的基因（如EPCAM）共定位。本研究为基于CEACAM5的纳米疫苗开发提供了全面的免疫基因组学理论依据，并根据肿瘤特异性和发育表达谱提出EPCAM和ATP10B作为共同靶点。
