摘要
目的利用生物信息学的方法分析肿瘤缺氧微环境对多发性骨髓瘤(multiplemyeloma,MM)转录组的影响,筛选差异基因,为探索细胞耐受缺氧环境的分子机制提供信息。方法从GEO数据库获得缺氧培养下的MM细胞株以及患者骨髓来源CD38阳性细胞的表达谱芯片,利用Limma包分析缺氧环境下一致性较好的差异基因,对这些差异基因进行GO和KEGG分析,并用TCGA数据库研究其表达水平与MM患者生存的关系。最后利用差异基因预测抑制缺氧微环境的潜在药物。结果针对2种数据集共筛选得到28个一致性较好的差异基因,这些基因主要参与细胞代谢途径、线粒体结构、自噬等,这可能与MM的缺氧耐受有关。生存分析显示:ANXA1、CLU、DPYSL3、CEP128、DDIT4、HMGCS1基因的高表达导致MM患者预后变差。CMAP分析提示PARP抑制剂可抑制缺氧相关信号通路。结论本研究利用生物信息学手段筛选得到了缺氧影响MM的差异基因,发现其中部分基因的高表达可导致MM患者预后变差,这可能与缺氧环境导致肿瘤细胞生存增强有关。PARP抑制剂可能成为缺氧抑制剂,与其他化疗药物联合使用实现更好的治疗效果。
OBJECTIVE To study the transcriptome of multiple myeloma(MM)affected by hypoxia and obtain the differential expressed genes(DEGs),which facilitate the mechanism of cellular hypoxic resistance.METHODS The expression profile of MM cell lines cultured under hypoxia and CD38 positive cells derived from patient bone marrow was obtained from GEO database.The DEGs with high consistent under hypoxia were analyzed by Limma package.GO and KEGG analysis were performed on the DEGs.Additionally,the expression levels of the DEGs on MM patient survival were studied by TCGA database.Finally,the potential drugs against hypoxia were predicted by the DEGs.RESULTS Totally 28 consistent DEGs were selected from the two datasets,which involved in cell metabolism,mitochondrial structure,autophagy and etc.These DEGs might contribute to the pro-survival effect in MM under hypoxia.The high expression of ANXA1,CLU,DPYSL3,CEP128,DDIT4,HMGCS1 suggested poor prognosis in MM patients which shorten the survival periods.The CMAP analysis suggested that PARP inhibitors could be used as a hypoxic antagonist.CONCLUSION DEGs under hypoxia in MM were obtained by bioinformatic analysis,some of which indicated the poor prognosis in MM patients.This may be associated with the pro-survival effect of hypoxia in tumor cells.PARP inhibitors may be used to inhibit the negative effect of hypoxia and combined with other chemotherapeutic drugs to achieve better therapeutic effect in MM.
作者
李颖
郑蓓
蒋慧芳
应茵
韩冰
张美玲
汪一帆
王强凤
李功华
LI Ying;ZHENG Bei;JIANG Huifang;YING Yin;HAN Bing;ZHANG Meiling;WANG Yifan;WANG Qiangfeng;LI Gonghuaa(Tongde Hospital of Zhejiang Province,Department of Pharmacy,Hangzhou 310012,China;Tongde Hospital of Zhejiang Province,Department of Hematology,Hangzhou 310012,China;Tongde Hospital of Zhejiang Province,Cancer Institute of Integrative Medicine,Hangzhou 310012,China;Department of Oncology,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2021年第2期148-155,共8页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省科技计划项目(2016F10026)
浙江省自然基金项目(LQY20H300001)
浙江省中医药科技计划项目(2019ZB028)
浙江省医药卫生科技计划面上项目(2018KY396)
浙江省药学会医院药学专项科研资助项目(2020ZYY25)。
关键词
多发性骨髓瘤
缺氧
肿瘤微环境
转录组
生物信息学
multiple myeloma
hypoxia
tumor microenvironment
transcriptome
bioinformatics
