CNV Primed lncRNAs Deregulation Contributes to Poor Prognosis in Colorectal Cancer

Abstract

Background: Increasing evidence suggests copy number variations(CNVs) are series of crucial genetic change elements exerting vital impact in initiation and progression of malignancies, including colorectal cancer(CRC). LncRNAs are supposed as well-known regulating factors in driving or inhibiting human oncogenesis and may be responsible for prognostic evaluation. However, how to construct communications between these two factors underlying CRC is largely unknown. Methods: Here, we introduce diverse machine learnings for investigating prognostic-related copy number changes of lncRNAs. R package-iCluster is initially applied to reveal five prognostic subtypes from 289 cases of CRC by integrating messenger RNA expression levels, DNA methylation and DNA copy numbers. Differentially expressed lncRNAs(DE-lncRNAs) and protein-coding genes(DE-PCGs) across five subtypes are determined based on DESeq2, and WGCNA is furtherly exploited to chase modules closely associated with clinical phenotypes. Profiling frequency change involved with lncRNAs, we wonder whether deregulated lncRNAs are accompanied with copy differences, as well as exploration for lncRNAs tightly implicated with clinical outcome. Findings: There are originally 27 modules obtained according to WGCNA on the foundation of 4253 DE-lncRNAs and 5808 DE-PCGs among five subtypes, of which only 4 modules are contacting frequently with more than three kinds of clinical features, namely, tan, blue, yellow, magenta. Comparing lncRNAs expression patterns between copy-deleted or copy-amplified and the normal samples, we identify 9 lncRNAs(FAM87A, LOC101927752, KBTBD11-OT1, LOC100287015, LOC101929066, CASC11, HM13-AS1, ABALON, NKILA), the expression levels of these 9 lncRNAs are significantly guided by copy number deletions or amplifications. Besides, survival probabilities imply total 10 lncRNAs(LOC101927604, LOC105377267, CASC15, LINC-PINT, CLDN10-AS1, C14orf132, LMF1, LINC00675, CCDC144NL-AS1, LOC284454) conspicuously contribute to poor prognosis in CRC. Interpretation: In conclusion, our research is interested in copy number changes of lncRNAs, not only expending the spectrum of CNVs concerned with CRC, but also perfecting the regulation network of lncRNAs in CRC. The main purpose is to provide novel biomarkers for prognostic managements of CRC patients. Funding Statement: This study was supported by the Jiangsu Health and Health Committee (H2018074), the Nantong Science and Technology Program (MS22015055), the National Natural Science Foundation of China (81702086), the Overseas Returnee Start Package (2015) from the Jiangsu Provincial Department of Human Resources and Social Security, the 226 Talent Training Project of Nantong City (The Fifth Batch), and the Elite Doctor Program of the Affiliated Hospital of Nantong University. Declaration of Interests: All authors declare that they have no conflicts of interest. Ethics Approval Statement: Ethics approval not required - publicly available data.