血小板源性生长因子B在胃癌组织的表达及其临床意义
The expression and clinical significance of platelet derived growth factor B in gastric cancer tissue
朱恒利 1邢文凤 1钱昆 2张碧涛 3黄国全 4孙建华3
作者信息
- 1. 湖北医药学院研究生院,十堰 442099
- 2. 重庆医科大学附属第一医院胃肠外科,重庆 400014
- 3. 恩施州中心医院胃肠外科,恩施 445099
- 4. 恩施州中心医院湖北硒与人体健康研究院,恩施 445099
- 折叠
摘要
目的 基于单细胞测序技术解析血小板源性生长因子B(PDGFB)在胃癌组织中的表达及其临床意义.方法 选用3对胃癌及配对的癌旁组织样本进行单细胞转录组测序(scRNA-seq).CellTypist对过滤后的单细胞表达数据进行亚群分类,使用Wilcoxon rank-sum对测序数据进行拟时序分析,探究不同细胞簇中PDGFB的差异表达.通过癌症基因组图谱(TCGA)及免疫组织化学技术(IHC)分析PDGFB在胃癌组织中的表达.收集68例胃癌患者临床数据,采用单因素和多因素Cox比例风险回归模型确定影响胃癌患者预后的独立因素.结果 scRNA-seq分析发现,PDGFB与4种促血管生成因子(FLT4、FLT1、TEK、KDR)在胃癌组织中均显著高表达(PDGFB与4种胃癌组织中的表达显著高于在癌旁组织中的表达,PDGFB在胃癌组织中的相对表达量为2.907,FLT4的相对表达量为2.293,FLT1的相对表达量为2.049,TEK的相对表达量为1.851,KDR的相对表达量为1.843,F=19.399,P＜0.01);不同细胞亚群的标记基因分析显示,PDGFB在内皮细胞中显著高表达(PDGFB在内皮细胞中的表达显著高于其他细胞,内皮细胞中相对表达量为2.533,成纤维细胞中相对表达量为0.872,巨噬细胞中相对表达量为1.391,组织干细胞中相对表达量为1.618,F=8.945,P＜0.01).TCGA和IHC分析表明,PDGFB在胃癌组织中的表达显著高于癌旁组织(PDGFB在胃癌组织中阳性率为66.18％(45/68),癌旁组织阳性率为17.65％(12/68),x2=32.89,P＜0.05),并且PDGFB高表达的患者术后5年生存率显著低于PDGFB低表达的患者(PDGFB高表达患者中位生存时间为20个月;PDGFB低表达患者中位生存时间为58个月,x=17.64,P＜0.05).多因素Cox回归分析显示,PDGFB的表达在胃癌患者的不同年龄、肿瘤大小、T分期、肿瘤分期均存在显著性相关性[风险系数(HR)=1.950,95％可信区间(CI)=1.101～3.455,P＜0.05;HR=5.102,95％CI=2.566～10.146,P＜0.05;HR=2.645,95％CI=1.116～6.268,P＜0.05;HR=3.985,95％CI=1.971～8.058,P＜0.05;HR=6.820,95％CI=1.552～29.967,P＜0.05],为总生存期相关的危险因素.结论 PDGFB在胃癌中高表达,并且PDGFB的高表达与胃癌患者的不良预后明显相关.
Abstract
Objective To analyze the expression and clinical significance of platelet derived growth factor B(PDGFB)in gastric cancer tissue based on single cell sequencing technology.Methods Single cell sequencing(scRNA-seq)was performed on three pairs of collected gastric cancer and adjacent tissue samples.CellTypist was used to classify subpopulations of filtered single cell expression data,and Wilcoxon was used to rank sum to perform quasi temporal analysis on sequencing data to explore the differ-ential expression of PDGFB in different cell clusters.The cancer genome atlas(TCGA)and immunohisto-chemistry(IHC)were performed on gastric cancer tissue to analyze the expression of PDGFB.The clinical data from 68 patients were collected and univariate and multivariate Cox proportional risk regression models were used to determine independent factors that affected the prognosis of gastric cancer patients.Results scRNA-seq analysis revealed that PDGFB and four angiogenic factors(FLT4,FLT1,TEK,KDR)were significantly overexpressed in gastric cancer tissue.The expression of PDGFB in four types of gastric cancer tissues was significantly higher than that in adjacent tissues.The relative expression level of PDGFB,FLT4,FLT1,TEK and KDR in gastric cancer tissue was 2.907,2.293,2.049,1.851 and 1.843 respec-tively(F=19.399,P＜0.01).Analysis of marker genes in different cell subpopulations revealed signifi-cant overexpression of PDGFB in endothelial cells.The expression of PDGFB in endothelial cells was sig-nificantly higher than that in other cells,with a relative expression level of 2.533 in endothelial cells,0.872 in fibroblasts,1.391 in macrophages,and 1.618 in tissue stem cells(F=8.945,P＜0.01).TCGA and IHC analysis found that the expression of PDGFB in gastric cancer tissue was significantly higher than that in adjacent tissues.The expression of PDGFB in gastric cancer tissue was higher than that in ad-jacent tissues.The positive rate of PDGFB in gastric cancer tissue was 66.18％(45/68),significantly higher than in adjacent tissues was[17.65％(12/68),x2=32.89,P＜0.05].The 5-year survival rate of patients with high PDGFB expression was significantly lower than that of patients with low PDGFB expres-sion.The median survival time of patients with high expression of PDGFB was 20 months,and that of pa-tients with low expression of PDGFB was 58 months(x2=17.64,P＜0.05).Multivariate Cox regression analysis showed that the expression of PDGFB was significantly correlated with age,tumor size,T stage,and tumor stage of gastric cancer patients[Hazard ratio(HR)=1.950,95％confidence interval(CI)=1.101-3.455,P＜0.05;HR=5.102,95％CI=2.566-10.146,P＜0.05;HR=2.645,95％CI=1.116-6.268,P＜0.05;HR=3.985,95％CI=1.971-8.058,P＜0.05;HR=6.820,95％CI=1.552-29.967,P＜0.05),which were risk factors related to overall survival.Conclusion PDGFB is highly ex-pressed in gastric cancer,and its high expression is associated with poor prognosis in gastric cancer pa-tients.
关键词
胃癌/血小板衍生生长因子B/单细胞测序技术/血管生成Key words
Gastric cancer/Platelet derived growth factor B/Single cell sequencing/Angio-genesis引用本文复制引用
基金项目
湖北省科技厅重大卫生项目(2022BCE024)
恩施州科技计划项目(D20200018)
出版年
2024
NETL
NSTL
万方数据