胃腺癌的体细胞突变图谱及RNA预后标志物
The Somatic Mutation Landscape and RNA Prognostic Markers in Stomach Adenocarcinoma.
作者信息
Zhang Xiulei, Zheng Peiming, Li Zhen, Gao Shanjun, Liu Guangzhi
机构信息
Department of Microbiome Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China.
Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Aug 4;13:7735-7746. doi: 10.2147/OTT.S263733. eCollection 2020.
PURPOSE
Stomach cancer is one of the highest incidence and mortality malignancies worldwide. Our study aimed to illustrate the somatic mutation landscape and identify molecular markers of stomach cancer.
MATERIALS AND METHODS
By integrated analysis of sequencing data and clinical data of stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA) database, we identified several susceptibility genes and novel molecular markers and validated their potential function by the starBase website. Further, we validated the clinical value of two candidate lncRNAs in collected STAD samples by RT-qPCR.
RESULTS
We illustrated the distributions of mutation frequencies and types to get the top 20 high-mutation frequency genes in STAD. We also found 2127 mRNAs, 129 miRNAs, and 170 lncRNAs that were differentially expressed. We identified four lncRNA-miRNA-mRNA ceRNAs (PVT1, MAGI2-AS3, MIR17HG, KCNQ1OT1). Besides, 27 mRNAs (PDE4C, ID1, AQP3, VCAN, FAP, NOX4, ANGPT2, SERPINE1, SPARC, PDGFRB, FN1, MFAP2, CSMD2, INHBA, COL10A1, MATN3, P4HA3, ADAMTS12, DGKI, OLFML2B, TMEM200A, FNDC1, CTHRC1, CHST1, F5, COL5A2, TUBB3) and two lncRNAs (MIR4458HG, LINC01235) showed a significant prognostic value, and their prognostic values were validated by the starBase website. What's more, the clinical values of MIR4458HG and LINC01235 were also demonstrated in collected STAD samples.
CONCLUSION
We constructed the lncRNA ceRNA networks and identified 20 high-mutation frequency genes and 29 prognostic markers (27 mRNAs and two lncRNAs).
目的
胃癌是全球发病率和死亡率最高的恶性肿瘤之一。我们的研究旨在阐明胃癌的体细胞突变图谱并鉴定其分子标志物。
材料与方法
通过对癌症基因组图谱（TCGA）数据库中胃腺癌（STAD）的测序数据和临床数据进行综合分析，我们鉴定了几个易感基因和新型分子标志物，并通过starBase网站验证了它们的潜在功能。此外，我们通过RT-qPCR验证了收集的STAD样本中两个候选lncRNA的临床价值。
结果
我们阐明了突变频率和类型的分布，以获得STAD中前20个高突变频率基因。我们还发现了2127个差异表达的mRNA、129个miRNA和170个lncRNA。我们鉴定了四个lncRNA-miRNA-mRNA ceRNA（PVT1、MAGI2-AS3、MIR17HG、KCNQ1OT1）。此外，27个mRNA（PDE4C、ID1、AQP3、VCAN、FAP、NOX4、ANGPT2、SERPINE1、SPARC、PDGFRB、FN1、MFAP2、CSMD2、INHBA、COL10A1、MATN3、P4HA3、ADAMTS12、DGKI、OLFML2B、TMEM200A、FNDC1、CTHRC1、CHST1、F5、COL5A2、TUBB3）和两个lncRNA（MIR4458HG、LINC01235）显示出显著的预后价值，并且它们的预后价值通过starBase网站得到验证。此外，MIR4458HG和LINC01235的临床价值也在收集的STAD样本中得到证实。
结论
我们构建了lncRNA ceRNA网络，并鉴定了20个高突变频率基因和29个预后标志物（27个mRNA和两个lncRNA）。
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