Epithelial-Mesenchymal Transition States and Metabolic Reprogramming Related Signatures Predict Prognosis and...

Epithelial-mesenchymal transition (EMT) and metabolic reprogramming have been shown to regulate HER2 targeted therapy resistance and tumor metastasis. We aimed to establish an EMT-associated and metabolic-related prognostic model in HER2-positive breast cancer.

mRNA expression and clinical information for HER2-positive breast cancer are downloaded from the TCGA database. The single sample gene set enrichment analysis score was used to generate EMT subtypes and identify EMT-related metabolic pathways. A prognostic risk score was developed based on the differentially expressed genes (DEGs) of the EMT-associated metabolic pathways using least absolute shrinkage and selection operator (LASSO) Cox regression and then validated in an external cohort (GSE96058).

The EMT enriched scores differentiated the OS in the HER2-positive breast cancer TCGA cohort (p = 0.023; HR, 0.38; 95% CI, 0.16-0.9), which was also associated with the carbohydrate, amino acid, nucleotide, and tricarboxylic acid (TCA) cycle pathways (p < 0.05). A total of 10 genes based on the DEGs between the metabolic groups were used to construct the prognosis model. Patients with low-risk metabolic scores showed longer OS compared to those with high-risk metabolic scores (p < 0.001; HR, 0.09; 95% CI, 0.03-0.31). The association between OS and the metabolism score remained significant in the multivariable Cox regression (p < 0.001; HR, 0.08; 95% CI, 0.03-0.22). Similar results were observed in the validation cohort (p = 0.002; HR, 0.34; 95% CI, 0.16-0.69).

EMT and metabolic reprogramming-related features are specific prognostic and potential therapeutic biomarkers for HER2-positive breast cancer patients, which warrant further studies.