[1]漆处梅,唐小龙.胰腺癌患者BZW1和BZW2表达水平及其与预后的相关性分析[J].医学信息,2022,35(21):26-33，39.[doi:10.3969/j.issn.1006-1959.2022.21.006]
　QI Chu-mei,TANG Xiao-long.Expression of BZW1 and BZW2 in Pancreatic Cancer and its Correlation with Prognosis[J].Journal of Medical Information,2022,35(21):26-33，39.[doi:10.3969/j.issn.1006-1959.2022.21.006]
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胰腺癌患者BZW1和BZW2表达水平及其与预后的相关性分析()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
35卷
期数:
2022年21期
页码:
26-33，39
栏目:
论著
出版日期:
2022-11-01

文章信息/Info

Title:
Expression of BZW1 and BZW2 in Pancreatic Cancer and its Correlation with Prognosis
文章编号:
1006-1959（2022）21-0026-09
作者:
漆处梅; 唐小龙
（1.达州市妇女儿童医院检验科，四川 达州 635000；2.滨州医学院第一临床医学院，山东 滨州 256600）
Author(s):
QI Chu-mei; TANG Xiao-long
(1.Department of Clinical Laboratory,Dazhou Women and Children’s Hospital,Dazhou 635000,Sichuan,China;2.The First Clinical Medical College,Binzhou Medical University,Binzhou 256600,Shandong,China)
关键词:
BZW1; BZW2; 胰腺癌; 预后标志物; 生物信息学
Keywords:
BZW1; BZW2; Pancreatic cancer; Prognostic markers; Bioinformatics
分类号:
R735.9
DOI:
10.3969/j.issn.1006-1959.2022.21.006
文献标志码:
A
摘要:
目的 探讨基本亮氨酸拉链和含W2结构域的蛋白质1、2（BZW1，BZW2）对胰腺癌患者的预后价值。方法 截至2021年12月，提取癌症基因组图谱-胰腺腺癌（TCGA-PAAD）数据库中4名健康和178例胰腺癌患者的RNA-seq数据和对应的临床信息以及基因型-组织表达数据库（GTEx）中167名健康人胰腺组织的RNA-seq数据。比较胰腺癌组织和正常组织中BZW1和BZW2的表达差异；受试者工作特征（ROC）曲线分析BZW1和BZW2在胰腺癌和正常组织中的预测准确性；时间依赖ROC曲线分析BZW1和BZW2的表达与时间相关的结局的预测效能；蛋白-蛋白互作网络（PPI）筛选与BZW1和BZW2相互作用的基因；京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析共表达基因的生物学功能和作用途径；免疫浸润分析BZW1和BZW2与免疫细胞的相关性；采用Kaplan-Meier曲线分析BZW1和BZW2的表达水平对胰腺癌患者预后的影响。结果 BZW1和BZW2在胰腺癌组织中的表达水平高于癌旁组织，差异有统计学意义（P＜0.05）；ROC曲线分析显示，BZW1和BZW2的曲线下面积（AUC）和95%置信区间（CI）分别为0.974（0.954~0.994）和0.944（0.918~0.970）；时间依赖ROC曲线分析显示，BZW1的表达预测胰腺癌患者1、3、5年总生存期的概率分别为0.611、0.673、0.825；BZW2的表达预测胰腺癌患者1、3、5年总生存期的概率分别为0.623、0.584、0.601；BZW1、BZW2及其共表达基因主要定位于细胞核膜上，具有翻译启动因子活性，参与细胞质翻译起始复合物的形成；BZW1与Th2细胞、T辅助细胞、Tcm细胞、Th1细胞、中性粒细胞和巨噬细胞呈正相关，与pDC细胞和Th17细胞呈负相关（P＜0.05）。BZW2仅与Th2细胞呈正相关，与NK细胞、TFH细胞、pDC、肥大细胞、细胞毒性细胞、iDC细胞、B细胞、T细胞、CD8 T 细胞、嗜酸性粒细胞、树突状细胞、Tem细胞呈负相关（P＜0.05）。高表达BZW1与患者的主要治疗结果有关，而高表达BZW2与T分期、M分期、肿瘤分期和病理分级有关（P＜0.05）。单因素Cox回归分析显示，BZW1、BZW2可作为预测胰腺癌患者总生存期的风险因子，高表达BZW1的胰腺癌患者拥有更短的总生存期、疾病特异性生存期和无进展间期，而高表达BZW2的胰腺癌患者拥有更短的总生存期和无进展间期。结论 BZW1和BZW2在胰腺癌组织中异常高表达，其水平升高与胰腺癌患者的不良预后有密切关系。因此，BZW1和BZW2可作为胰腺癌患者潜在的预后标志物。
Abstract:
Objective To investigate the prognostic value of basic leucine zipper and W2 domain-containing proteins 1 and 2 (BZW1, BZW2) in patients with pancreatic cancer.Methods As of December 2021, RNA-seq data and corresponding clinical information of 4 healthy and 178 pancreatic cancer patients in the Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) database and RNA-seq data of 167 healthy human pancreatic tissues in the Genotype-Tissue Expression Database (GTEx) were extracted. Compare the expression of BZW1 and BZW2 in pancreatic cancer and normal tissues; the predictive accuracy of BZW1 and BZW2 in pancreatic cancer and normal tissues was analyzed by ROC curve.Time-dependent ROC curve was used to analyze the predictive efficacy of BZW1 and BZW2 expression in time-related outcomes. protein-protein interaction network (PPI) was used to screen the genes interacting with BZW1 and BZW2; the biological functions and pathways of co-expressed genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The correlation between BZW1 and BZW2 and immune cells was analyzed by immune infiltration. Kaplan-Meier curve was used to analyze the effect of BZW1 and BZW2 expression levels on the prognosis of patients with pancreatic cancer.Results The expression levels of BZW1 and BZW2 were higher in pancreatic cancer tissues than in normal tissues, and the differences were statistically significant (P<0.05); ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (CI) for BZW1 and BZW2 were 0.974 (0.954-0.994) and 0.944 (0.918-0.970), respectively. The time-dependent ROC curves showed that the expression of BZW1 predicted the overall survival of pancreatic cancer patients at 1-, 3-, and 5-years with probabilities of 0.611, 0.673 and 0.825, respectively. In addition, the expression of BZW2 predicted the overall survival of pancreatic cancer patients at 1-, 3-, and 5-years with probabilities of 0.623, 0.584 and 0.601, respectively.BZW1, BZW2 and their co-expressed genes were involved in the formation of the cytoplasmic translation initiation complex by localizing to the cell nuclear membrane and having translation initiation factor activity. BZW1 was positively correlated with Th2 cells, T helper cells, Tcm cells, Th1 cells, neutrophils and macrophages, and negatively correlated with pDC cells and Th17 cells (P<0.05). BZW2 was positively correlated with Th2 cells only, and positively correlated with NK cells, TFH cells, pDC, mast cells,cytotoxic cells, iDC cells, B cells, T cells, CD8 T cells, eosinophils, dendritic cells, and Tem cells were negatively correlated (P<0.05). What’s more, high expression of BZW1 correlated with the primary therapy outcome, and high expression of BZW2 correlated with T stage, M stage, pathologic stage and histologic grade were related. Univariate Cox regression analysis showed that BZW1 and BZW2 could be used as a risk factor to predict overall survival of pancreatic cancer patients. Pancreatic cancer patients with high expression of BZW1 had shorter overall survival, disease-specific survival, and progression-free interval, while pancreatic cancer patients with high BZW2 expression had shorter overall survival and progression-free interval.Conclusion BZW1 and BZW2 are abnormally highly expressed in pancreatic cancer tissues, and their elevated levels are closely associated with poor prognosis of patients. Hence, BZW1 and BZW2 can be used as potential prognostic markers for patients with pancreatic cancer.

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更新日期/Last Update: 1900-01-01