Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes

Kai Wang,Yang Yao,Kai Song,Yanqiao Zhang,Chao Liu,Wenyuan Zhao,Huiting Xiao,Jing Yang,Jiashuai Zhang,Zhigang Ma

doi:10.1038/s41416-020-0902-y

Abstract

BackgroundOur laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature.MethodsBased on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature.ResultsAn EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related.ConclusionsThe EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.

Highlights

Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC)
In this study, based on the hypothesis that the stage II patients who relapse after surgery could be primarily attributed to micrometastasis, we developed a gene pair signature using EMTrelated genes for predicting post-surgery relapse risk of stage II CRC patients
The immune-related gene pair signature (IRGPI) was constructed by relative expression orderings (REOs)-based individualised prognostic method, it did not perform predictive capacity for the RNA-seq dataset from TCGA, and it was validated without considering the specificity of stage

Summary

Introduction

Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). This signature was not applicable for RNA-sequencing datasets. RESULTS: An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. CONCLUSIONS: The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients. Colorectal cancer (CRC) ranks third in terms of incidence, but second in terms of cancer-related death worldwide.[1] Treatment decision and prognosis assessment mainly depend on the pathological stage of the tumour.[2] about 20% patients of stage II CRC will relapse after curative surgery.[3] some other factors were proposed for therapy decisions. These clinicopathological risk factors do not adequately distinguish between patients who have high or low risk of relapse, and lead to over- or underdiagnosis.[5]

Objectives

Methods

Results

Conclusion