Nanovaccine targeting in colorectal cancer: a multi-dataset analysis of CEA expression, cytokine profiles, and co-expressed genes.

Q2 Medicine
Medicine and Pharmacy Reports Pub Date : 2025-07-01 Epub Date: 2025-07-30 DOI:10.15386/mpr-2917
Razvan-Septimiu Zdrehus, Cristina Mitrea, Lucian Mocan
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引用次数: 0

Abstract

Background: 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.

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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结直肠癌纳米疫苗靶向:CEA表达、细胞因子谱和共表达基因的多数据集分析
背景:癌胚抗原(CEA/CEACAM5)是一种在包括结直肠癌(CRC)在内的上皮恶性肿瘤中过表达的肿瘤相关抗原。虽然其诊断和治疗相关性已得到承认,但其免疫学背景和作为纳米疫苗靶点的潜力仍未得到充分探索。目的:本研究旨在通过整合转录组学和空间数据来识别免疫相关的共表达生物标志物和潜在的治疗靶点,从而实现基于cea的纳米疫苗的合理设计和改进。方法:利用TCGA-COAD、GEO和空间数据集(GSE207843、GSE226997)的转录组学数据进行综合生物信息学分析,并辅以差异基因表达分析(GSE245218)。CEACAM5的表达与细胞因子谱(IL10、IFNG、TNF、IL1B、IL12A、IL4)、免疫细胞浸润(通过xCell)和共表达网络相关。Spearman ρ > 0.75基因优先作为候选疫苗,并通过癌胎表达和文献整理进行评估。结果:CEACAM5的表达与IFNG、IL10、TNF和IL1B呈负相关,提示其潜在的免疫抑制表型。xCell分析显示CEACAM5与效应免疫群体(包括CD8+ T细胞和NK细胞)呈负相关。空间转录组学证实CEACAM5在肿瘤上皮中区隔化,细胞因子重叠最小。共表达分析确定EPCAM和ATP10B为高可信度候选者。胚胎与成人的差异分析(GSE245218)证实了它们的癌胎表达模式。基因本体分析显示抗菌体液免疫通路下调。结论:CEACAM5定义了一种独特的免疫沉默肿瘤表型,并与其他疫苗相关基因(如EPCAM)共定位。该研究为ceacam5导向的纳米疫苗开发提供了全面的免疫基因组学基础,并基于肿瘤特异性和发育性表达谱提出了EPCAM和ATP10B作为共同靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Medicine and Pharmacy Reports
Medicine and Pharmacy Reports Medicine-Medicine (all)
CiteScore
3.10
自引率
0.00%
发文量
63
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