A Robust 6-lncRNA Prognostic Signature for Predicting the Prognosis of Patients With Colorectal Cancer Metastasis.

Shuyuan Li,Yinan Su,Boxue Wang,Shuo Chen,Lin Zhang,Xipeng Zhang

doi:10.3389/fmed.2020.00056

Abstract

Objective: Our study aimed to construct a robust long non-coding RNA (lncRNA) prognostic signature for colorectal cancer (CRC) metastasis.Methods: Differentially expressed lncRNAs were identified between metastatic CRC and non-metastatic CRC samples from The Cancer Genome Atlas Database (TCGA) using the edgeR package. The differentially expressed lncRNAs with prognosis of patients with CRC metastasis were identified by univariate Cox regression analysis, followed by a stepwise multivariate Cox regression model. The survminer package in R was used to identify the optimal cutoff point for high-risk and low-risk groups. The receiver operating characteristic (ROC) curves were plotted to assess this signature. To explore potential signaling pathways associated with these lncRNAs, Gene Set Enrichment Analysis (GSEA) was performed.Results: A 6-lncRNA signature was built based on the lncRNA expression profile for CRC metastasis. The optimal cutoff value was used to classify high-risk and low-risk groups using the survminer package. The high-risk groups could have poorer survival time than the low-risk groups. ROC curve result indicated that this lncRNA signature had high sensitivity and accuracy. GSEA analysis results showed that the six lncRNAs were significantly enriched in several CRC metastasis-related signaling pathways such as “cell cycle,” “DNA replication,” “mismatch repair,” “oxidative phosphorylation,” “regulation of autophagy,” and “insulin signaling pathway.”Conclusion: Our study constructed a 6-lncRNA model for predicting the survival outcomes of patients with CRC metastasis, which could become potential prognostic biomarkers, and therapeutic targets for CRC metastasis.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, which is the leading cause of cancer-related deaths worldwide [1, 2]
Sixty-seven differentially expressed long non-coding RNAs (lncRNAs) were identified between distant metastasis (M1) and non-metastasis (M0) CRC according to adjusted p < 0.05, including 46 upregulated and 21 downregulated lncRNAs (Supplementary Table 1)
To identify differentially expressed lncRNAs associated with prognosis of patients with CRC metastasis, we performed overall survival analysis of 67 differentially expressed lncRNAs using a univariate Cox proportional hazard regression model in the entire set (n = 85)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, which is the leading cause of cancer-related deaths worldwide [1, 2]. Tumor metastasis is a multistep cellular biology process [5]. Despite significant advances in the diagnosis and treatment of CRC, metastasis remains the leading cause of CRCrelated deaths [7]. Conventional treatments for metastatic CRC include resection, radiation therapy, and chemotherapy. These treatments have limitations such as insufficient resection and local recurrence. Radiation therapy and chemotherapy lack of tumor specificity and concomitant cytotoxic effects. It is difficult to treat recurrent CRC cells by conventional chemotherapy or radiation therapy. It is important to identify genes associated with CRC metastasis

Methods

Results

Discussion

Conclusion