A novel epithelial‐mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer

Abstract

Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log‐rank test and multivariate Cox regression analysis according to EMT‐related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high‐risk patients who need an intensive follow‐up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.

Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer

“…Furthermore, SLC2A3 may regulate the expression of PD-L1 [ 15 ]. An EMT signature performs well in predicting the overall survival, and the model is associated with immune infiltration, proving its potential role in regulating immune status [ 16 ]. Additionally, other EMT-immune-related biomarkers, for example, LIPH, CDH11, SETBP1, and so on, also have prognostic value in different cancers [ 17 – 23 ].…”

Identification of a novel prognostic signature correlated with epithelial‐mesenchymal transition, N6‐methyladenosine modification, and immune infiltration in colorectal cancer

“…19 There is a growing body of studies to establish the prognostic signature based the genes related to EMT or m6A modification. 9,[20][21][22] In the present study, our findings will not only further highlight the clinical application of EMT and m6A modification, but also provide novel drug targets for individualized treatment.…”

“…The m6A modification is a novel molecular mechanism participating in CRC development through regulating the various RNA processes such as splicing, translation, and degradation 19 . There is a growing body of studies to establish the prognostic signature based the genes related to EMT or m6A modification 9,20–22 . In the present study, our findings will not only further highlight the clinical application of EMT and m6A modification, but also provide novel drug targets for individualized treatment.…”

Retinoblastoma-Binding Protein 5 Regulates H3K4 Methylation Modification to Inhibit the Proliferation of Melanoma Cells by Inactivating the Wnt/β-Catenin and Epithelial-Mesenchymal Transition Pathways

“…EMT-related markers include N-cadherin, E-cadherin, vimentin, and Snail, which have been documented in lots of cancers, such as breast [58], colorectal [59], oral [60], lung [61], pancreatic [62], melanoma [51,[63][64][65], and liver cancers [66]. EMT-related markers were associated with tumor initiation, invasion, metastasis, and resistance to therapy [47,[67][68][69].…”