Enhancer-derived long non-coding RNAs CCAT1 and CCAT2 at rs6983267 has limited predictability for early stage colorectal carcinoma metastasis

Sci Rep. 2021 Jan 11;11(1):404. doi: 10.1038/s41598-020-79906-7.

Abstract

Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and 2, was associated with worse prognosis in colorectal cancer (CRC). Nevertheless, their role in predicting metastasis in early-stage CRC is unclear. We measured the expression of CCAT1, CCAT2 and their oncotarget, c-Myc, in 150 matched mucosa-tumour samples of early-stage microsatellite-stable Chinese CRC patients with definitive metastasis status by multiplex real-time RT-PCR assay. Expression of CCAT1, CCAT2 and c-Myc were significantly up-regulated in the tumours compared to matched mucosa (p < 0.0001). The expression of c-Myc in the tumours was significantly correlated to time to metastasis [hazard ratio = 1.47 (1.10-1.97)] and the risk genotype (GG) of rs6983267, located within CCAT2. Expression of c-Myc and CCAT2 in the tumour were also significantly up-regulated in metastasis-positive compared to metastasis-negative patients (p = 0.009 and p = 0.04 respectively). Nevertheless, integrating the expression of CCAT1 and CCAT2 by the Random Forest classifier did not improve the predictive values of ColoMet19, the mRNA-based predictor for metastasis previously developed on the same series of tumours. The role of these two lncRNAs is probably mitigated via their oncotarget, c-Myc, which was not ranked high enough previously to be included in ColoMet19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • Biomarkers, Tumor
  • CCAT1 long noncoding RNA, human
  • RNA, Long Noncoding
  • long non-coding RNA CCAT2, human