Copy number variations primed lncRNAs deregulation contribute to poor prognosis in colorectal cancer

Abstract

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.

A signature related to lung adenocarcinoma prognosis: A study based on TCGA database

“…Furthermore, lncRNAs act as ceRNA or miRNA sponges, representing an extensive form of gene expression regulation at the post-transcriptional level [28]. Out of four lncRNAs (LINC00460, LINC00330, DGCR5, and C14orf132) in the signature, C14orf132 and LINC00330 were found to be related to the prognosis of colorectal cancer and bladder cancer, respectively [29][30]. In this study, high expression of C14orf132 could prolong the survival of LUAD patients, but its specific mechanism of action needs to be explored.…”

Genomic Alterations Characterization in Colorectal Cancer Identifies a Prognostic and Metastasis Biomarker: FAM83A|IDO1

“…Elegant efforts have demonstrated multifarious genomic alterations were critical to the prognosis and target therapy of CRC [31][32][33][34][35]. We sought to better delineate the molecular diversity of CRC via mutation signatures that re ect different mutational processes, such as spontaneous deamination of 5methylcytosine (signature 1), defective DNA mismatch repair (signature 6, 15, and 20), recurrent POLE somatic mutations (signature 10), and tobacco chewing habit (signature 29).…”

Copy Number Variation: Methods and Clinical Applications

“…Pushing the limits of CNV detection revealed that they are widespread in human populations with a 5-10% difference of genomic sequences between normal individuals [1][2][3]. As a significant aspect of our heterogeneity, CNVs may disrupt gene function or alter gene dosage by direct gain or loss of coding sequences [4], but several indirect mechanisms including alteration of non-coding RNAs [5,6] and topologically associated domains [7] have been described. Since these may affect the phenotype, CNVs may threaten the ability to survive or, on the contrary, enhance chances of survival in disadvantageous environments [8].…”

“…. 2021, 11, 819 2 of 16 alter gene dosage by direct gain or loss of coding sequences [4], but several indirect mechanisms including alteration of non-coding RNAs [5,6] and topologically associated domains [7] have been described. Since these may affect the phenotype, CNVs may threaten the ability to survive or, on the contrary, enhance chances of survival in disadvantageous environments [8].…”