吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (5): 1268-1279.doi: 10.13481/j.1671-587X.20230521

• 临床研究 • 上一篇    

细胞焦亡分型和APOD预测胃癌患者预后作用的生物信息学分析

崔海康1,张旭东1,李晓宁1,杨希1,杨兰1,2,张文杰1,2()   

  1. 1.石河子大学医学院病理系,新疆 石河子 832002
    2.新疆地方与民族高发病教育部重点实验室,新疆 石河子 832002
  • 收稿日期:2022-11-07 出版日期:2023-09-28 发布日期:2023-10-26
  • 通讯作者: 张文杰 E-mail:zhangwj82@qq.com
  • 作者简介:崔海康(1995-),男,河北省石家庄市人,在读硕士研究生,主要从事胃癌病理和分子诊断学方面的研究。
  • 基金资助:
    国家自然科学基金项目(81260301);国家科技支撑计划项目(2009BAI82B02)

Bioinformatics analysis on predition effect of subtypes of cell pyroptosis and APOD on prognosis of gastric cancer patients

Haikang CUI1,Xudong ZHANG1,Xiaoning LI1,Xi YANG1,Lan YANG1,2,Wenjie ZHANG1,2()   

  1. 1.Department of Pathology, School of Medicial Sciences, Shihezi University, Shihezi 832002, China
    2.Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi 832002, China
  • Received:2022-11-07 Online:2023-09-28 Published:2023-10-26
  • Contact: Wenjie ZHANG E-mail:zhangwj82@qq.com

摘要:

目的 寻找胃癌(GC)患者的预后标志物,实现GC的早诊早治,为提高GC患者的生存率提供依据。 方法 从癌症基因图谱(TCGA)数据库和GSE84437数据集下载407和433例GC患者的临床数据和转录组数据并合并,根据细胞焦亡相关基因的表达水平和ConsensusClusterPlus数据包对GC组织样本进行聚类分型,分为A分型(342例)和B分型(465例),将GC患者按照载脂蛋白D(APOD)水平分为低表达组和高表达组。采用survminer数据包比较不同分型患者预后的差异,采用ssGSEA算法比较不同分型患者免疫浸润的差异,采用Lasso回归和Cox回归构建GC患者预后风险模型,对模型基因进行临床性状过滤,采用公共数据库分析APOD在癌旁正常组织和GC组织中表达水平的差异,采用基因富集分析(GSEA)分析APOD的京都基因与基因组百科全书(KEGG)信号通路富集情况,采用CIBERSORT 算法评估免疫细胞含量并分析其与APOD表达的相关性,采用在线网站分析APOD的药物敏感性。 结果 2种细胞焦亡分型患者预后比较差异有统计学意义(P=0.002);A分型患者中22种免疫细胞含量均高于B分型(P<0.01);不同年龄(P<0.01)、N分期(P=0.04)患者2种细胞焦亡分型百分率差异有统计学意义。公共数据库分析,在GC患者肿瘤组织中APOD表达水平低于癌旁正常组织;生存分析,高表达组GC患者预后较低表达组差;临床相关性分析,不同T分期患者APOD表达水平比较差异有统计学意义(P<0.05);GSEA分析,高表达组在细胞黏附通路、白细胞内皮迁移通路和缝隙连接通路富集;免疫浸润分析,高表达组中滤泡辅助T淋巴细胞、CD4+记忆激活T淋巴细胞、静息自然杀伤(NK)细胞和中性粒细胞含量少于低表达组;APOD与CXC趋化因子配体12(CXCL12)(r=0.500,P<0.01)、转化生长因子B1(TGFB1)(r=0.313,P<0.01)、CC趋化因子配体 19(CCL19)(r=0.518,P<0.01)和CX3C趋化因子受体1(CX3CR1)(r=0.444,P<0.01)呈正相关关系;药物敏感性分析,APOD与AZD-7762、KW-2449和TG-101348呈正相关关系(0<r<0.3,P<0.05)。 结论 依据焦亡分型可以较好地评估GC患者的预后;APOD可以成为GC新的预后标志物和治疗靶点。

关键词: 胃肿瘤, 细胞焦亡, 载脂蛋白D, 生存, 预后, 免疫浸润

Abstract:

Objective To seek the prognostic markers for the gastric cancer (GC) patients, and to achieve the early diagnosis and treatment of GC, and to provide the evidence for improving the survival rate of the GC patients. Methods The clinical data and transcriptome data of 407 and 433 GC patients were downloaded from the The Cancer Genome Atlas(TCGA) Database and GSE84437 Dataset, and merged; the GC tissue samples were classified and typed based on the expression levels of cell death-related genes and the ConsensusClusterPlus Package,and were divided into type A(342 cases) and type B(465 cases);the GC patients were divided into low expression group and high expression group according to the expression level of apolipoprotein D(APOD);the survminer Data Package was used to compare the differences in prognosis of the patients with different subtypes;the ssGSEA Algorithm was used to compare the differences in immune cell infiltration of the patients with different subtypes; Lasso regression and Cox regression were used to construct the prognostic risk model for the GC patients; the clinical characteristics of model genes were filtered;the differential expression of APOD in adjacent normal tissue and GC tissue was analyzed by Public Databases;GSEA analysis was used to assess the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment of APOD; the CIBERSORT Algorithm was used to evaluate the correlation between the content of immune cells and expression of APOD;the online website was used to analyze the drug sensitivity of APOD. Results There was statistically significant difference in prognosis of the patients with two subtypes of cell pyroptosis(P=0.002); the levels of 22 kinds of immune cells of the patients with type A were higher than those with type B(P<0.01); there were statistically significant differences in the percentages of two subtypes of cell pyroptosis of the patients with different ages (P<0.01) and N stages (P=0.04). The Public Databases analysis results showed that the expression of APOD in tumor tissue of the GC patients was lower than that in adjacent normal tissue; the survival results showed that compared with low expression group,the patients in high expression group had poorer prognosis; the clinical correlation analysis results showed that there were significant differences in the APOD expression of the patients with different T stage (P<0.05); the GSEA analysis results showed that high expression group enriched in the cell adhesion pathways, leukocyte endothelial migration pathways, and gap junction pathways; the immune infiltration analysis results showed that the contents of follicular helper T lymphocytes, CD4+ memory activated T lymphocytes, resting NK cells, and neutrophils in high expression group were lower than those in low expression group; APOD had positive correlations with CXC chemokine ligand 12(CXCL12)(r=0.500,P<0.01),transforming growth factor beta 1(TGFB1) (r=0.313,P<0.01),chemokine CC chemokine ligand 19(CCL19)(r=0.518,P<0.01),and CX3C chemokine receptor 1(CX3CR1)(r=0.444,P<0.01);the drug sensitivity analysis results showed that there were positive correlations between APOD and AZD-7762, KW-2449, and TG-101348(0<r<0.3,P<0.05). Conclusion Cell pyroptosis subtypes can effectively evaluate the prognosis of the GC patients; APOD can be regarded as the novel prognostic marker and therapeutic target for GC.

Key words: Gastric neoplasm, Cell pyroptosis, Apolipoprotein D, Survival, Prognosis, Immune infiltration

中图分类号: 

  • R735.2