目的 4号染色体开放阅读框19（chromosome 4 open reading frame 19,C4orf19）是一种功能尚不明确的蛋白,本研究旨在探讨C4orf19在结肠腺癌（colon adenocarcinoma,COAD）中的表达水平、生物学功能、对肿瘤微环境的影响,同时通过药物敏感性分析,筛选针对不同C4orf19表达水平患者的潜在有效治疗药物,为COAD的精准治疗提供新的理论依据和实验基础。方法 通过TCGA-COAD数据集和Gene Expression Omnibus（GEO）数据集分析C4orf19的表达情况及其对患者预后的影响。通过ESTIMATE算法和CIBERSORT算法评估C4orf19表达对COAD患者肿瘤微环境的影响。通过免疫组化检测C4orf19的表达并分析其与免疫细胞浸润的相关性。通过GO、KEGG和GSEA通路富集分析C4orf19参与调控的生物学过程和信号通路。基于oncoPredict算法分析C4orf19的表达与COAD患者药物敏感性之间的关系。结果 C4orf19在COAD中表达下调且与患者预后不良相关。肿瘤微环境分析显示,C4orf19低表达组肿瘤微环境中的静息期记忆CD4+ T细胞浸润减少,M 0型巨噬细胞浸润增加。通路富集分析表明,C4orf19主要参与调控细胞色素P450介导的药物代谢和外源性物质代谢。药物敏感性分析显示,C4orf19低表达组患者对达沙替尼、SN-38及Navitoclax更敏感,而C4orf19高表达组患者对吉西他滨、5-氟尿嘧啶、培利替尼和西妥昔单抗更敏感。结论 C4orf19低表达在COAD中促进了抑制性肿瘤免疫微环境的形成,并降低肿瘤细胞对部分化疗药物的敏感性。
Abstract
Objective Chromosome 4 open reading frame 19 (C4orf19) is a protein with poorly understood functions. This study aims to explore the expression, biological functions, and impact of C4orf19 on the tumor microenvironment in colon adenocarcinoma (COAD). Additionally, through drug sensitivity analysis, we aim to screen potential effective therapeutic drugs for patients with different C4orf19 expression levels, thereby providing a new theoretical and experimental basis for precision therapy of COAD. Methods The expression of C4orf19 and its impact on patient prognosis were analyzed using the TCGA-COAD dataset and the Gene Expression Omnibus (GEO) dataset. The ESTIMATE algorithm and CIBERSORT algorithm were used to assess the influence of C4orf19 expression on the tumor microenvironment in COAD patients. Immunohistochemistry was conducted to detect the expression of C4orf19 and its correlation with immune cell infiltration. GO, KEGG, and GSEA pathway enrichment analyses were performed to identify the biological processes and signaling pathways regulated by C4orf19. The relationship between C4orf19 expression and drug sensitivity in COAD patients was analyzed using the oncoPredict algorithm. Results C4orf19 expression was downregulated in COAD and associated with poor patient prognosis. Tumor microenvironment analysis revealed that the low C4orf19 expression group had decreased infiltration of resting memory CD4+ T cells and increased infiltration of M0 macrophages in the tumor microenvironment. Pathway enrichment analysis indicated that C4orf19 is mainly involved in regulating cytochrome P450-mediated drug metabolism and xenobiotic metabolism. Drug sensitivity analysis showed that patients with low C4orf19 expression were more sensitive to dasatinib, SN-38, and navitoclax, while patients with high C4orf19 expression were more sensitive to gemcitabine, 5-fluorouracil, pelitinib, and cetuximab. Conclusion Low C4orf19 expression promotes the formation of a suppressive tumor immune microenvironment in COAD and reduces the sensitivity of tumor cells to certain chemotherapeutic drugs.
关键词
结肠腺癌 /
C4orf19 /
肿瘤微环境 /
药物敏感性
Key words
colon adenocarcinoma /
C4orf19 /
tumor microenvironment /
drug sensitivity
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基金
国家自然科学基金项目“核受体PXR在洛伐他汀促进三阴性乳腺癌干细胞对多柔比星敏感性中的作用及机制”（82173374）; 湖南省自然科学基金项目“ALKBH5通过m6A修饰RBPJ调控肿瘤相关巨噬细胞极化抑制结直肠癌进展的机制研究”（2024JJ9523）
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