Ma G F, Zhang R F, Ying K J, Wang D
Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):578-85.
This study was performed to evaluate the therapeutic effect of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer (NSCLC).
Dataset GSE39345 from patients who underwent cisplatin-gemcitabine combination chemotherapy and normal controls was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using Limma package and divided into 3 datasets: unique DEGs in NSCLC before chemotherapy vs. control samples (dataset A), common DEGs (dataset B), unique DEGs in NSCLC after chemotherapy vs. control samples (dataset C). Enrichment analysis was to identify functions or pathways of DEGs. Protein-protein interaction (PPI) analysis was to identify hub nodes and interacting pairs in dataset C and constructed into PPI network using Cytoscape software, followed by screening of small molecules using Connectivity Map.
Herein, 230 unique DEGs in dataset A, 584 common DEGs in dataset B and 1562 unique DEGs in dataset C were obtained. The 230 DEGs were significantly enriched in methylation and positive regulation of cell differentiation; the 584 DEGs were significantly enriched in positive regulation of cell differentiation and cytokine-cytokine receptor interaction pathway; the 1562 DEGs were enriched in functions associated with defense response. RELA and PLCB3 correlated with PLCE1 and INADL were hub nodes in the PPI network. Cefoperazone was the small molecule negatively correlated with DEGs.
Chemotherapy could prevent genes from aberrant methylation, partially restore cell differentiation process, fail to regulate cytokine-cytokine receptor interaction and induce weakened defense response. Cefoperazone could be used as a supplementary drug.
本研究旨在评估顺铂 - 吉西他滨联合化疗对晚期非小细胞肺癌（NSCLC）的治疗效果。
从基因表达综合数据库下载接受顺铂 - 吉西他滨联合化疗患者及正常对照的数据集GSE39345。使用Limma软件包鉴定差异表达基因（DEG），并将其分为3个数据集：化疗前NSCLC中的独特DEG与对照样本（数据集A）、共同DEG（数据集B）、化疗后NSCLC中的独特DEG与对照样本（数据集C）。富集分析用于鉴定DEG的功能或通路。蛋白质 - 蛋白质相互作用（PPI）分析用于鉴定数据集C中的枢纽节点和相互作用对，并使用Cytoscape软件构建成PPI网络，随后使用连通性图谱筛选小分子。
在此，在数据集A中获得230个独特DEG，数据集B中获得584个共同DEG，数据集C中获得1562个独特DEG。230个DEG在甲基化和细胞分化的正调控中显著富集；584个DEG在细胞分化的正调控和细胞因子 - 细胞因子受体相互作用通路中显著富集；1562个DEG在与防御反应相关的功能中富集。与PLCE1和INADL相关的RELA和PLCB3是PPI网络中的枢纽节点。头孢哌酮是与DEG呈负相关的小分子。
化疗可防止基因异常甲基化，部分恢复细胞分化过程，无法调节细胞因子 - 细胞因子受体相互作用并诱导防御反应减弱。头孢哌酮可作为辅助药物使用。
