Abstract

Colon adenocarcinoma (COAD) is a common type of colon cancer, and post-operative recurrence and metastasis may occur in COAD patients. This study is designed to build a risk score system for COAD patients. The Cancer Genome Atlas (TCGA) dataset of COAD (the training set) was downloaded, and GSE17538 and GSE39582 (the validation sets) from Gene Expression Omnibus database were obtained. The differentially expressed RNAs (DERs) were analyzed by limma package. Using survival package, the independent prognosis-associated long non-coding RNAs (lncRNAs) were selected for constructing risk score system. After the independent clinical prognostic factors were screened out using survival package, a nomogram survival model was constructed using rms package. Furthermore, competitive endogenous RNA (ceRNA) regulatory network and enrichment analyses separately were performed using Cytoscape software and DAVID tool. Totally 404 DERs between recurrence and non-recurrence groups were identified. Based on the six independent prognosis-associated lncRNAs (including H19, KCNJ2-AS1, LINC00899, LINC01503, PRKAG2-AS1, and SRRM2-AS1), the risk score system was constructed. After the independent clinical prognostic factors (Pathologic M, pathologic T, and RS model status) were identified, the nomogram survival model was built. In the ceRNA regulatory network, there were three lncRNAs, four miRNAs, and 77 mRNAs. Additionally, PPAR signaling pathway and hedgehog signaling pathway were enriched for the mRNAs in the ceRNA regulatory network. The risk score system and the nomogram survival model might be used for predicting COAD recurrence. Besides, PPAR signaling pathway and hedgehog signaling pathway might affect the recurrence of COAD patients.

Highlights

  • As a common malignancy occurring in the colon, colon cancer is divided into adenocarcinoma, undifferentiated carcinoma, and mucinous adenocarcinoma [1]

  • The long non-coding RNAs (lncRNAs) cytoskeleton regulator RNA (CYTOR) facilitates epithelial-to-mesenchymal transition (EMT) and metastasis in colon cancer via interacting with β-catenin, which predicts poor prognosis and may be promising therapeutic target of colon cancer [9, 10]. These results suggested that lncRNAs might be used as biomarkers for predicting the prognosis of colon cancer

  • The results showed that the grouping based on the risk score system had significant correlations with the actual recurrence prognosis in the The Cancer Genome Atlas (TCGA) dataset and the validation sets (Figure 2)

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Summary

Introduction

As a common malignancy occurring in the colon, colon cancer is divided into adenocarcinoma, undifferentiated carcinoma, and mucinous adenocarcinoma [1]. The 5years survival rate of colon cancer after radical operation is about 60–70%, and the main reasons leading to the failure of surgical treatment are post-operative recurrence and metastasis [4, 5]. The lncRNA cytoskeleton regulator RNA (CYTOR) facilitates epithelial-to-mesenchymal transition (EMT) and metastasis in colon cancer via interacting with β-catenin, which predicts poor prognosis and may be promising therapeutic target of colon cancer [9, 10]. These results suggested that lncRNAs might be used as biomarkers for predicting the prognosis of colon cancer

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