首页|香叶基香叶基焦磷酸合成酶在肺鳞状细胞癌中的表达及临床意义

香叶基香叶基焦磷酸合成酶在肺鳞状细胞癌中的表达及临床意义

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
  • 维普
目的·利用生物信息学和免疫组织化学法探究在肺鳞状细胞癌(lung squamous cell carcinoma,LUSC)组织中香叶基香叶基焦磷酸合成酶(geranylgeranyl diphosphate synthase 1,GGPS1)的表达及其临床意义.方法·首先从UCSC Xena平台下载LUSC组织与配对正常组织的转录组数据,使用R语言进行数据标准化和差异表达分析,并利用UALCAN数据库进行验证;采用UALCAN和LinkedOmics数据库分析LUSC患者中GGPS1表达与临床病理特征关系;利用Kaplan-Meier Plotter数据库探究LUSC患者GGPS1表达对预后的影响.应用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)回归分析筛选基因相关系数及风险评分.通过列线图和校正曲线评价GGPS1对LUSC的诊断价值.采用STRING、GeneMANIA数据库构建GGPS1蛋白质相互作用(protein-protein interaction,PPI)网络.运用R语言挑选与GGPS1 相关差异基因,并进行基因本体论(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析.采用免疫组织化学法检测LUSC患者GGPS1表达情况,并分析其与临床病理特征和预后的相关性.结果·通过TIMER2.0数据库检索到GGPS1在多数肿瘤中表达均升高,且在LUSC中呈高表达.UCSC Xena、UALCAN数据库中GGPS1在LUSC的表达高于癌旁组织(均P<0.05).UALCAN和LinkedOmics数据库发现GGPS1在指标分期较晚患者中的表达水平更高,且Kaplan-Meier Plotter数据库显示LUSC患者GGPS1高表达总生存期(overall survival,OS)较短(P<0.05).基于LASSO回归评估LUSC患者有较好的风险预测效能.构建LUSC患者的个体化预测模型具有最佳预测准确度.GO、KEGG结果显示,GGPS1相关基因主要与蛋白质代谢、调节脂质和胆固醇代谢过程、尼古丁成瘾、磷脂酰肌醇3激酶(phosphatidylinositol3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPAR)信号通路等有关.GGPS1的代谢功能可能促进肿瘤发生.免疫组化结果提示GGPS1主要定位于细胞质中,且LUSC组织中表达高于癌旁组织(P<0.05),GGPS1高表达与LUSC患者肿瘤大小、淋巴结转移和TNM分期有关(均P<0.05),且GGPS1表达高的患者OS明显短于低表达者(P=0.000).多因素Cox回归分析提示GGPS1可作为LUSC的独立预后因素.结论·相较于正常肺组织,GGPS1在LUSC中表达显著升高,尤其在肿瘤体积较大、淋巴结转移阳性及晚期的患者中表达升高更明显;且GGPS1过表达是LUSC患者预后差的独立预测因子.GGPS1有望成为新的LUSC诊治和预防的分子靶点.
Expression and clinical significance of geranylgeranyl diphosphate synthase1(GGPS1)in lung squamous cell carcinoma
Objective·To investigate the expression and clinical significance of geranylgeranyl diphosphate synthase1(GGPS1)in lung squamous cell carcinoma(LUSC)by bioinformatics and immunohistochemistry.Methods·Firstly,the transcriptome data of LUSC tissues and paired normal tissues were downloaded from UCSC Xena platform.The data were standardized and differentially expressed by R language,and verified by UALCAN database.UALCAN and LinkedOmics databases were used to analyze the relationship between GGPS1 expression and clinicopathological features in LUSC patients.The Kaplan-Meier Plotter database was used to explore the effect of GGPS1 expression on prognosis in LUSC patients.The least absolute shrinkage and selection operator(LASSO)regression analyses were applied to screen gene correlation coefficients and risk scores.The diagnostic value of GGPS1 for LUSC was evaluated by nomogram and calibration curve.The protein-protein interaction(PPI)network of GGPS1 was constructed by using STRING and GeneMANIA databases.R language was used to select the differential genes related to GGPS1,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed.The expression of GGPS1 in LUSC patients was detected by immunohistochemistry,and its correlation with clinicopathological features and prognosis was analyzed.Results·Through the TIMER2.0 database,it was found that GGPS1 expression was increased in most tumors and was highly expressed in LUSC.The expression of GGPS1 in LUSC was higher than that in adjacent tissues in UCSC Xena and UALCAN databases(both P<0.05).It was found that the expression level of GGPS1 was higher in patients with late stage in UALCAN and LinkedOmics databases,and the overall survival(OS)of LUSC patients with high expression of GGPS1 was shorter(P<0.05)in the Kaplan-Meier Plotter database.Assessment of LUSC patients based on LASSO regression had good risk prediction efficacy.Constructing an individualised prediction model for LUSC patients has the best prediction accuracy.The results of GO and KEGG showed that GGPS1-related genes were mainly related to protein metabolism,regulation of lipid and cholesterol metabolism,nicotine addiction,phosphatidylinositol3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),peroxisome proliferator-activated receptors(PPAR)signaling pathway and so on.The metabolic function of GGPS1 may promote tumorigenesis.The results of immunohistochemistry showed that GGPS1 was mainly located in the cytoplasm,and the expression of GGPS1 in LUSC tissues was higher than that in adjacent tissues(P<0.05).The high expression of GGPS1 was related to tumor size,lymph node metastasis and TNM stage of LUSC patients(all P<0.05),and the OS of patients with high expression of GGPS1 was significantly shorter than that of patients with low expression(P=0.000).Multivariate Cox regression analysis suggested that GGPS 1 could be used as an independent prognostic factor for LUSC.Conclusion·Compared with normal lung tissue,the expression of GGPS1 in LUSC is significantly increased,especially in patients with large tumor volume,positive lymph node metastasis and advanced stage.GGPS1 overexpression is an independent predictor of poor prognosis in LUSC patients.GGPS1 is expected to become a new molecular target for the diagnosis,treatment and prevention of LUSC.

geranylgeranyl diphosphate synthase 1(GGPS1)lung squamous cell carcinoma(LUSC)bioinformaticsimmunohistochemistryclinical significance

王鑫、王晓霞、李彦庆、郑永鑫、乌杰、任猛、贾向东、许天祥

展开 >

内蒙古科技大学包头医学院研究生院,包头 014060

内蒙古自治区人民医院腹部肿瘤外科,呼和浩特 010017

内蒙古自治区人民医院重症医学科,呼和浩特 010017

内蒙古医科大学研究生院,呼和浩特 010000

展开 >

香叶基香叶基焦磷酸合成酶 肺鳞状细胞癌 生物信息学 免疫组织化学 临床意义

内蒙古自治区自然科学基金内蒙古自治区自然科学基金内蒙古自治区自然科学基金内蒙古自治区自然科学基金内蒙古自治区人民医院博士科研启动基金内蒙古自治区卫生健康科技计划内蒙古自治区卫生健康科技计划内蒙古自治区卫生健康科技计划内蒙古自治区人民医院院内项目内蒙古医科大学联合项目内蒙古医科院公立医院科研联合基金科技项目内蒙古医科院公立医院科研联合基金科技项目

2023LHMS080522023MS080192019MS080852018LH080022020BS062022010122022010112017030112020YN06YKD2022LH0152023GLLH00122023GLLH0038

2024

10.3969/j.issn.1674-8115.2024.03.003

上海交通大学学报(医学版)
上海交通大学

上海交通大学学报(医学版)

CSTPCD北大核心
影响因子：0.826
ISSN：1674-8115
年,卷(期)：2024.44(3)
  • 29