Liu Huimin, Gu Xiaoyu, Wang Guihua, Huang Ying, Ju Shaoqing, Huang Jianfei, Wang Xudong
Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Aging (Albany NY). 2019 Aug 22;11(16):6089-6108. doi: 10.18632/aging.102168.
Copy number variations (CNVs) are crucial genetic change elements in malignancies, and lncRNAs deregulation induced by genomic and epigenomic aberrations plays key driving role in tumorigenesis, including colorectal cancer (CRC). However, effects of CNVs associated with lncRNAs in CRC is largely unknown. Here, we perform integrative analysis considering messenger RNA expression levels, DNA methylation and DNA copy numbers from 289 cases of CRC specimens. There are five prognostic subtypes of CRC determined by multi-omics integration, and differentially expressed lncRNAs (DE-lncRNAs) are acquired among five subtypes and normal cases. Finally, CNVs pattern matched with DE-lncRNAs reveals a signature including 10 lncRNAs (LOC101927604, LOC105377267, CASC15, LINC-PINT, CLDN10-AS1, C14orf132, LMF1, LINC00675, CCDC144NL-AS1, LOC284454), conspicuously contributing to poor prognosis in CRC, which can be validated in another independent dataset. Together, our research is interested in copy number changes relevant with lncRNAs, not only expending the spectrum of CNVs, but also perfecting the regulation network of lncRNAs in CRC. The main purpose is to provide novel biomarkers for prognostic managements of CRC patients.
拷贝数变异（CNVs）是恶性肿瘤中关键的基因改变元件，由基因组和表观基因组畸变诱导的长链非编码RNA（lncRNAs）失调在肿瘤发生过程中起关键驱动作用，包括结直肠癌（CRC）。然而，与lncRNAs相关的CNVs在CRC中的作用在很大程度上尚不清楚。在此，我们对289例CRC标本的信使RNA表达水平、DNA甲基化和DNA拷贝数进行了综合分析。通过多组学整合确定了CRC的五种预后亚型，并在五种亚型和正常病例中获得了差异表达的lncRNAs（DE-lncRNAs）。最后，与DE-lncRNAs匹配的CNVs模式揭示了一个包含10个lncRNAs的特征（LOC101927604、LOC105377267、CASC15、LINC-PINT、CLDN10-AS1、C14orf132、LMF1、LINC00675、CCDC144NL-AS1、LOC284454），显著导致CRC预后不良，这在另一个独立数据集中得到了验证。总之，我们的研究关注与lncRNAs相关的拷贝数变化，不仅扩展了CNVs的范围，还完善了CRC中lncRNAs的调控网络。主要目的是为CRC患者的预后管理提供新的生物标志物。
