Abstract
Competing endogenous RNAs (ceRNAs) are a newly proposed RNA interaction mechanism that has been associated with the tumorigenesis, metastasis, diagnosis, and predicting survival of various cancers. In this study, we constructed a ceRNA network in colorectal cancer (CRC). Then, we sought to develop and validate a composite clinicopathologic–genomic nomogram using The Cancer Genome Atlas (TCGA) database. To construct the ceRNA network in CRC, we analyzed the mRNAseq, miRNAseq data, and clinical information from TCGA database. LncRNA, miRNA, and mRNA signatures were identified to construct risk score as independent indicators of the prognostic value in CRC patients. A composite clinicopathologic–genomic nomogram was developed to predict the overall survival (OS). One hundred sixty-one CRC-specific lncRNAs, 97 miRNAs, and 161 mRNAs were identified to construct the ceRNA network. Multivariate Cox proportional hazards regression analysis indicated that nine-lncRNA signatures, eight-miRNA signatures, and five-mRNA signatures showed a significant prognostic value for CRC. Furthermore, a clinicopathologic–genomic nomogram was constructed in the primary cohort, which performed well in both the primary and validation sets. This study presents a nomogram that incorporates the CRC-specific ceRNA expression profile, clinical features, and pathological factors, which demonstrate its excellent differentiation and risk stratification in predicting OS in CRC patients.
Highlights
The third most common type of cancer is colorectal cancer (CRC), which is ranked as the second most frequent cause of cancer-related death worldwide (Bray et al, 2018)
We aimed to apply a systematic approach to evaluate the clinical usefulness of CRC-related signatures and construct a composite clinicopathologic–genomic nomogram by integrating factors with potential prognostic value based on The Cancer Genome Atlas (TCGA) database
By comparing the CRC group with the normal group, we identified the significant DElncRNAs, DEmiRNAs, and DEmRNAs using the edgeR package in R software
Summary
The third most common type of cancer is colorectal cancer (CRC), which is ranked as the second most frequent cause of cancer-related death worldwide (Bray et al, 2018). Recent research highlights the key functions of lncRNAs in the regulation of biological processes These include genomic imprinting, immune response, cell cycle and apoptosis, immune response, and different types of cancer (Beermann et al, 2016; Fang and Fullwood, 2016). Current research indicates the function of lncRNAs as miRNA sponges and competing endogenous RNAs (ceRNAs). This reduces the availability of miRNAs for mRNA target binding (Salmena et al, 2011; Tay et al, 2014). The ceRNA hypothesis underlines the interaction of the RNA with miRNA response elements (MREs) This type of crosstalk and competition in the RNA occurs among mRNAs and lncRNAs (Zhang et al, 2016a). Studies with larger sample sizes should be conducted on CRC’s association with lncRNA-mediated ceRNA network in a whole-genome sequence
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