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一项关于维生素D受体(VDR)作为免疫检查点抑制剂治疗预测生物标志物与结肠腺癌免疫浸润相关性的研究。

A study of the association of vitamin D receptor (VDR) as a predictive biomarker for immune checkpoint inhibitor therapy with immune invasion in colon adenocarcinoma.

作者信息

Chao Guanqun, Lin Ailing, Bao Yang

机构信息

Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University, China.

Department of General Practice, Sir Run Run Shaw Hospital, Zhejiang University, China.

出版信息

J Pharm Biomed Anal. 2025 Jan 1;252:116510. doi: 10.1016/j.jpba.2024.116510. Epub 2024 Oct 5.

DOI:10.1016/j.jpba.2024.116510
PMID:39378759
Abstract

Colon adenocarcinoma(COAD) is a primary and aggressive malignancy with the fifth highest mortality rate among cancers, and it is important to discover new strategies. The online database was used to analyze the correlation between Vitamin D receptor (VDR) and COAD, and further explore the immune infiltration and related gene networks.The expression and methylation levels of VDR was analyzed by using Timer database, GEPIA platform and UALCAN database. GeneMANIA database was used to analyze and obtain gene networks that are closely linked to VDR. UALCAN database was used to score the gene effects of VDR in colorectal cancer cell lines. The cBioPortal database was used for the detection of gene mutations. The survival curve analysis was carried out using the GEPIA database. The relationship between VDR expression and immune cell infiltration was analyzed by using the timer database and TISIDB database. TISIDB database was used to obtain VDR-related drug targets.The expression of VDR was significantly lower in COAD(p<0.05). The methylation level of VDR was significantly higher in COAD (p<0.05). The gene mutation rate of VDR in COAD was 2 %. OS and DFS were not associated with changes in the VDR gene in patients with COAD. VDR expression was correlated with CD4+T cell infiltration, macrophage infiltration, neutrophil infiltration, and dendritic cell infiltration. VDR has a clear correlation with ADORA2A, BTLA, CD160, CD244, CD274, CD96, CSF1R, CTLA4, HAVCR2, IL10, IDO1, LAG3, LGALS9, PDCD1, PDCD1LG2, PVRL2, TGFB1, TGFBR1, TIGIT and VTCN1.The expression of VDR is associated with immune infiltration in patients with COAD. VDR may be a new candidate biomarker for determining the level of immune infiltration and predicting immune checkpoint inhibitor therapy.

摘要

结肠腺癌(COAD)是一种原发性侵袭性恶性肿瘤,在癌症中死亡率排名第五,因此发现新的治疗策略很重要。利用在线数据库分析维生素D受体(VDR)与COAD之间的相关性,并进一步探索免疫浸润及相关基因网络。通过Timer数据库、GEPIA平台和UALCAN数据库分析VDR的表达和甲基化水平。利用GeneMANIA数据库分析并获得与VDR密切相关的基因网络。使用UALCAN数据库对VDR在结肠癌细胞系中的基因效应进行评分。利用cBioPortal数据库检测基因突变。使用GEPIA数据库进行生存曲线分析。通过Timer数据库和TISIDB数据库分析VDR表达与免疫细胞浸润之间的关系。利用TISIDB数据库获取与VDR相关的药物靶点。COAD中VDR的表达显著降低(p<0.05)。COAD中VDR的甲基化水平显著升高(p<0.05)。COAD中VDR的基因突变率为2%。COAD患者的总生存期(OS)和无病生存期(DFS)与VDR基因的变化无关。VDR表达与CD4+T细胞浸润、巨噬细胞浸润、中性粒细胞浸润和树突状细胞浸润相关。VDR与ADORA2A、BTLA、CD160、CD244、CD274、CD96、CSF1R、CTLA4、HAVCR2、IL10、IDO1、LAG3、LGALS9、PDCD1、PDCD1LG2、PVRL2、TGFB1、TGFBR1、TIGIT和VTCN1有明显相关性。VDR的表达与COAD患者的免疫浸润相关。VDR可能是一种新的候选生物标志物,用于确定免疫浸润水平和预测免疫检查点抑制剂治疗效果。

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