摘要
目的基于胰腺癌相关的高通量基因表达(GEO)和癌症基因组图谱(TCGA)数据,采用生存相关算法筛选并验证参与胰腺癌患者生存的关键预后基因。方法采用GEO数据库2个胰腺癌基因芯片(Microarray)和TCGA数据库胰腺癌转录组测序(RNA-seq)数据,利用Kaplan-Meier(KM)分析和Cox比例风险模型进行生存相关基因的过滤并取目的基因交集;对交集基因进行多因素回归分析与临床相关性分析筛选预后相关基因;对预后相关基因进行通路富集分析和CIBERSORT免疫富集分析寻找其调控胰腺癌的潜在分子机制。结果本研究借助TCGA和GEO数据库中包含的生存信息与临床特征的3个胰腺癌数据集,筛选得到了5个与胰腺癌生存相关的基因(CDO 1、DCBLD 2、FAM 83 A、ITGA 3和SLC 16 A 3),且多因素Cox回归分析和临床相关性分析表明,CDO 1高表达是胰腺癌预后的保护性因素,其抑癌作用与抑制肿瘤细胞恶性生物学行为和促进胰腺癌抗肿瘤活性免疫细胞浸润相关。结论本研究首次提出了CDO 1是与胰腺癌预后显著相关的保护性基因,并发现CDO 1的抑癌机制与抗肿瘤免疫微环境形成密切相关,为后续胰腺癌基础研究与临床治疗提供了新靶点。
Objective Based on Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database,survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients.Methods Two pancreatic cancer gene chips(Microarray)from the GEO database and transcriptome sequencing(RNA-seq)from the TCGA database were used to filter the survival-related genes using Kaplan-Meier(KM)analysis and Cox risk model,and the target genes were intersected.Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer.Results In this study,five survival-related genes(i.e.,CDO 1,DCBLD 2,FAM 83 A,ITGA 3 and SLC 16 A 3)were screened out.Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO 1 expression was a protective factor for pancreatic cancer prognosis,and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer.Conclusion This study suggests that CDO 1 is a potential tumor suppress gene of pancreatic cancer,and the tumor inhibition effect of CDO 1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.
作者
龚梦元
王琦琦
朱泽恩
仵正
王铮
钱伟琨
GONG Mengyuan;WANG Qiqi;ZHU Zeen;WU Zheng;WANG Zheng;QIAN Weikun(Department of Hepatobiliary Surgery,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Pancreatic Disease Center of Xi’an Jiaotong University,Xi’an 710061,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2023年第5期717-724,共8页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金青年基金项目(No.82103117)。
关键词
胰腺癌
生存相关基因
CDO1
免疫微环境
pancreatic cancer
survival-related gene
CDO 1
immune microenvironment
