Abstract

Increasing evidence has suggested that dysregulated lncRNA expression played important roles in the development and progression of human cancers. Although prognostic roles of lncRNAs have been recognized for colon cancer (CC) patients, the search for novel lncRNA biomarkers potentially involved in CC progression is an urgent and still largely unmet medical need. In this study, we evaluated the lncRNA expression changes during the progression of CC by analyzing two cohorts of previously published expression profiles of CC patients and identified hundreds of differentially expressed lncRNAs. Then we identified eight lncRNAs that closely associated with the progression of CC patients from a large number of significantly altered lncRNAs using random forest supervised classification algorithm. Finally, an SVM-based lncRNA risk classifier was developed to discriminate high-risk CC patients from persons with early-stage and validated in both the training dataset and testing dataset by survival analysis and five-fold cross-validation strategy. Our pathway enrichment analysis based on protein-coding genes that are co-expressed with lncRNAs, suggested that variation in expression of eight lncRNAs biomarkers might affect critical pathways involved in CC progression. With further validation, these eight lncRNAs might have significant implications for the clinical management of CC patients with early stage and improve our understanding of cancer progression.

Highlights

  • Colon cancer (CC) is one of the most common types of human cancers and is the major cause of cancerrelated death worldwide [1]

  • Prognostic roles of long noncoding RNAs (lncRNAs) have been recognized for CC patients, the search for novel lncRNA biomarkers potentially involved in CC progression is an urgent and still largely unmet medical need

  • The GSE37892 patient dataset was chosen as a training dataset for the detection of lncRNA biomarkers

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Summary

Introduction

Colon cancer (CC) is one of the most common types of human cancers and is the major cause of cancerrelated death worldwide [1]. The fact that early-stage CC patients with an initial treatment with surgery are known to still have a recurrence rate of 20%–30% and are likely to progress into malignancy [2]. Systemic treatment of early-stage patients with high-risk for disease progression attempts to prevent disease progression and improve patients’ outcome. It is an urgent need to identify high-risk patients who are likely to progress into malignancy at an early stage of cancer development. A large number of lncRNAs are found to be differentially expressed in various types of human cancer. Prognostic roles of lncRNAs have been recognized for CC patients, the search for novel lncRNA biomarkers potentially involved in CC progression is an urgent and still largely unmet medical need

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