Wu Xiaofen, Ruan Lei, Yang Yi, Mei Qi
Department of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, China.
Biol Res. 2017 Feb 23;50(1):6. doi: 10.1186/s40659-017-0108-9.
This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC).
We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis.
We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-β signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%.
Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.
本研究旨在调查与参与非小细胞肺癌（NSCLC）的癌相关成纤维细胞（CAF）相关的基因表达变化。
我们下载了GEO系列GSE22862，其中包含15个CAF和正常成纤维细胞样本的匹配基因表达值，以及包含4个匹配NSCLC样本的SNP基因分型的系列GSE27289。使用R中的limma软件包鉴定CAF样本中的差异表达基因。然后，我们使用鉴定出的差异表达基因进行基因本体（GO）和通路富集分析以及蛋白质-蛋白质相互作用（PPI）网络构建。此外，使用等位基因特异性拷贝数分析来分析CAF细胞内的异常细胞分数、倍性、等位基因特异性拷贝数和杂合性缺失（LOH）。
我们在CAF和正常成纤维细胞样本之间获得了545个差异表达基因。上调基因主要参与细胞迁移的正调控和细胞外区域等GO术语，而下调基因参与肺发育和细胞外区域。包括骨形态发生蛋白4（BMP4）和转化生长因子β3（TGFB3）在内的多个基因参与TGF-β信号通路。包括BMP4、TGFBI和基质Gla蛋白（MGP）在内的基因是枢纽基因。此外，未发现BMP4和MGP的LOH事件，鞘氨醇激酶1（SPHK1）的LOH事件为70%，TGFBI的LOH事件为40%。
我们的数据表明，BMP4、MGP、TGFBI和SPHK1可能在CAF相关的NSCLC中起重要作用，它们的异常表达和高LOH频率可作为NSCLC中CAF的诊断靶点。
