Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1298
Peer-review started: December 1, 2019
First decision: December 23, 2019
Revised: January 8, 2020
Accepted: March 9, 2020
Article in press: March 9, 2020
Published online: March 28, 2020
Processing time: 117 Days and 21.9 Hours
Colorectal cancer (CRC) is one of the most prevalent tumors worldwide. Recently, long noncoding RNAs (lncRNAs) have been identified to influence tumorigenesis and tumor progression through acting as competing endogenous RNAs (ceRNAs). It is difficult to extract prognostic lncRNAs and useful bioinformation in most of ceRNA networks constructed before.
To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in CRC.
We systematically analyzed RNA transcriptome profile and clinical information of 506 CRC patients in the Cancer Genome Atlas database and constructed a prognostic related ceRNA network including 9 lncRNAs, 44 mRNAs, and 30 miRNAs. In addition, a four-lncRNA model was constructed by multivariate Cox regression analysis, which could be an independent prognostic model in CRC. The risk score for each patient was calculated and 506 patients were divided into high/low-risk groups (253 for each group) based on the median risk score.
The results of survival analysis showed that patients with a high risk score had a poor survival rate. In addition, the predictive value of the four-lncRNA model was evaluated in GSE38832. Furthermore, the patients’ survival probabilities could be better predicted when combing the risk score and clinical features. GSEA results verified that a number of cancer-related signaling pathways were definitely enriched with high risk score in CRC. Finally, we validated a novel lncRNA (LINC00488) that has not been reported before by using qRT-PCR in 22 paired CRC patient’s tumor tissues compared with adjacent non-tumor tissues.
The major findings reported in this study could be considered a preliminary attempt to explore the prognostic lncRNAs, miRNAs, and mRNAs in CRC. Therefore, our understanding of lncRNA related ceRNA regulatory mechanism could provide a potential diagnostic target for CRC patient.
Further validation in other independent datasets is required to evaluate the general applicability of the signature in CRC. Additional studies are needed to confirm the biological functions of the lncRNAs, miRNAs, and mRNAs of the ceRNA network in CRC.