Identification and Validation of EMT-Related lncRNA Prognostic Signature for Colorectal Cancer

Danfeng Li; Xiaosheng Lin; Binlie Chen; Zhiyan Ma; Yongming Zeng; Huaiming Wang

doi:10.3389/fgene.2021.723802

Identification and Validation of EMT-Related lncRNA Prognostic Signature for Colorectal Cancer

Front Genet. 2021 Sep 22:12:723802. doi: 10.3389/fgene.2021.723802. eCollection 2021.

Authors

Danfeng Li¹, Xiaosheng Lin¹, Binlie Chen^{2

1}, Zhiyan Ma^{2

1}, Yongming Zeng¹, Huaiming Wang¹

Affiliations

¹ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
² Medical College, Shantou University, Shantou, China.

Abstract

Background: This study aimed to explore the biological functions and prognostic role of Epithelial-mesenchymal transition (Epithelial-mesenchymal transition)-related lncRNAs in colorectal cancer (CRC). Methods: The Cancer Genome Atlas database was applied to retrieve gene expression data and clinical information. An EMT-related lncRNA risk signature was constructed relying on univariate Cox regression, Least Absolute Shrinkage and Selector Operation (LASSO) and multivariate Cox regression analysis of the EMT-related lncRNA expression data and clinical information. Then, an individualized prognostic prediction model based on the nomogram was developed and the predictive accuracy and discriminative ability of the nomogram were determined by the receiver operating characteristic curve and calibration curve. Finally, a series of analyses, such as functional analysis and unsupervised cluster analysis, were conducted to explore the influence of independent lncRNAs on CRC. Results: A total of 581 patients were enrolled and an eleven-EMT-related lncRNA risk signature was identified relying on the comprehensive analysis of the EMT-related lncRNA expression data and clinical information in the training cohort. Then, risk scores were calculated to divide patients into high and low-risk groups, and the Kaplan-Meier curve analysis showed that low-risk patients tended to have better overall survival (OS). Multivariate Cox regression analysis indicated that the EMT-related lncRNA signature was significantly associated with prognosis. The results were subsequently confirmed in the validation dataset. Then, we constructed and validated a predictive nomogram for overall survival based on the clinical factors and risk signature. Functional characterization confirmed this signature could predict immune-related phenotype and was associated with immune cell infiltration (i.e., macrophages M0, M1, Tregs, CD4 memory resting cells, and neutrophils), tumor mutation burden (TMB). Conclusions: Our study highlighted the value of the 11-EMT-lncRNA signature as a predictor of prognosis and immunotherapeutic response in CRC.

Keywords: EMT-related lncRNA; colorectal cancer; nomogram; prognostic; signature.