An Integrated Three-Long Non-coding RNA Signature Predicts Prognosis in Colorectal Cancer Patients.

Yuhang Liu,Bingxin Liu,Yuan Yin,Zhaohui Huang,Zehua Bian,Guoying Jin,Yuyang Feng,Bojian Fei,Xue Wang,Jia Zhang

doi:10.3389/fonc.2019.01269

Yuhang Liu, Bingxin Liu + Show 8 more

Open Access

https://doi.org/10.3389/fonc.2019.01269

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Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide, whose morbidity and mortality gradually increased. Here, we aimed to identify and access prognostic long non-coding RNAs (lncRNAs) associated with overall survival (OS) in CRC. Firstly, RNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and 439 CRC patients were enrolled as a training set. Univariate Cox analysis and the least absolute shrinkage and selection operator analysis (LASSO) were performed to identify the prognostic lncRNAs. Multivariable Cox regression analysis was used to establish a prognostic risk formula including three lncRNAs (AP003555.2, AP006284.1, and LINC01602). The low-risk group had a better OS than the high-risk group (P < 0.0001), and the areas under the receiver operating characteristic curve (AUCs) of 3- and 5-year OS were 0.712 and 0.674, respectively. Then, we evaluated the signature in a clinical validation set which were collected from the Affiliated Hospital of Jiangnan University. Compared with the low-risk group, patients' OS were found to be significantly worse in the high-risk group (P = 0.0057). The AUCs of 3- and 5-year OS were 0.701 and 0.694, respectively. Finally, we constructed an lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) network to explore the potential function of three differentially expressed lncRNAs (DElncRNAs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DElncRNAs were involved with several cancer-related pathways. In summary, our data provide evidence that the three-lncRNA signature could serve as an independent biomarker to predict prognosis in CRC. This study will also suggest that these three lncRNAs potentially participate in the progression of CRC.

Highlights

Colorectal cancer (CRC) is a worldwide public health problem with the fourth highest incidence and second highest mortality in malignant tumors [1]
A growing number of studies have demonstrated that dysregulated lncRNAs are involved in the progression of CRC and might be potential biomarkers for diagnosis, treatment, FIGURE 6 | The prognostic value of integrated three long non-coding RNAs in the training set and clinical validation set, respectively
A novel three-lncRNA signature was constructed for predicting overall survival (OS) of CRC patients

Summary

Introduction

Colorectal cancer (CRC) is a worldwide public health problem with the fourth highest incidence and second highest mortality in malignant tumors [1]. LncRNA Prognostic Signature for CRC improved in recent years, prognosis remains unsatisfactory due to individual differences [6]. It is necessary to find sensitive and precise biomarkers to better predict survival and prognosis of CRC patients. Our previous study identified SNHG6 as an oncogene and predicted poor prognosis in CRC [19]; we found that the lncRNA LINC00152 could promote CRC cell proliferation and metastasis [20]. Another study from our group suggested that lncRNAFEZF1-AS1 promoted CRC cell proliferation and metastasis [21]. The biological function of lncRNAs in CRC is still not wellknown, and a systematic study incorporating multiple lncRNAs’ expression is still needed for improving the predictive accuracy of CRC prognosis

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