BICDL1 预测结直肠癌的不良预后，并与甲基化和免疫渗透相关
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摘要
背景：Bicaudal-D (BICD) Family Like Cargo Adaptor 1（BICDL1）是神经元发育过程中分子机制的重要组成部分。然而，BICDL1 在癌症中的作用尚未见报道。通过生物信息学分析，我们系统地评估了 BICDL1 在 CRC 中的潜在作用：从基因表达总库（GEO）、基因型-组织表达（GTEx）和癌症基因组图谱（TCGA）数据库中检索结直肠癌（CRC）和正常组织样本。采用卡普兰-梅耶（K-M）分析、提名图、COX分析和接收者操作特征曲线（ROC）来评估预后能力。还利用 cBioPortal 进行了相关性分析，以探讨 BICDL1 的 mRNA 表达与甲基化水平之间的相关性，以及免疫浸润与 BICDL1 之间的相关性。研究人员通过 RT-qPCR 和 Western 印迹分析了人类结直肠癌细胞系和正常结肠上皮细胞的 BICDL1 表达水平：结果：在TCGA和GES 74602数据集中，BICDL1在CRC组织中的表达高于正常组织（p <0.001）。Kaplan-Meier生存分析显示，BICDL1高表达的患者总生存率（OS）较低（1.53，95%置信区间：1.07- 2.17，P=0.019）。ROC曲线显示，BICDL1在诊断中具有较高的特异性和效率（AUC=0.919，CI：0.895- 0.943）。BICDL1的表达水平与Treg（R=0.146，p <0.001）、TFH（R=0.080，p=0.043）、NK CD56bright细胞（R=0.149，p <0.001）、aDC（R=0.095，p=0.016）和T辅助细胞浸润（R=- 0.084，p=0.034）的浸润水平显著相关。BICDL1 的表达与甲基化水平呈负相关（R2=0.134，p <0.001），CRC 患者的甲基化水平低于正常人（p=0.036）。与正常结肠上皮细胞（NCM460）相比，BICDL1 mRNA及其蛋白在CRC细胞系（SW620）中的表达水平明显升高（p < 0.001）：结论：BICDL1可能是评估免疫浸润水平和CRC预后的潜在生物标志物。本文章由计算机程序翻译，如有差异，请以英文原文为准。
BICDL1 Predicts Poor Prognosis and is Correlated with Methylation and Immune Infiltration in Colorectal Cancer
Background: Bicaudal-D (BICD) Family Like Cargo Adaptor 1 (BICDL1) is an essential component of the molecular mechanism during neuronal development. However, BICDL1 has not been reported in cancer. Using bioinformatics analysis, we systematically evaluated the potential role of BICDL1 in CRC.
Methods: Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan–Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells.
Results: BICDL1 had a higher expression in CRC tissues than in normal tissues (p < 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07– 2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895– 0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p < 0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p < 0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=− 0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p < 0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p < 0.001).
Conclusion: BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.
Methods: Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan–Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells.
Results: BICDL1 had a higher expression in CRC tissues than in normal tissues (p < 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07– 2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895– 0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p < 0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p < 0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=− 0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p < 0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p < 0.001).
Conclusion: BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.
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