Prognostic biomarker NRG2 correlates with autophagy and epithelial‑mesenchymal transition in breast cancer.

Breast cancer (BRCA) is a leading cause of death in women worldwide, accounting for 31% of female cancer. Autophagy plays a crucial role in cancer progression, however, the function of autophagy-related gene neuroregulatory protein 2 (NRG2) in BRCA and its underlying molecular mechanisms remain unclear. In the present study, the expression of the NRG2 gene in BRCA was significantly down-regulated compared with the normal controls. The low expression level of NRG2 was related to poor survival rate of BRCA. The receiver operating characteristic curve of NRG2 showed a good diagnostic value for distinguishing BRCA from normal tissues (AUC=0.932). GO-KEGG analysis and GSEA enrichment analysis showed that NRG2 and its regulated genes were enriched in autophagy-related and immune-related pathways, and NRG2 was positively correlated with a number of immune cells and immune checkpoint genes. In addition, knockdown of NRG2 significantly promoted the proliferation, invasion and migration of BRCA cells. The autophagy marker, LC3-II and epithelial-mesenchymal transition (EMT) marker, vimentin were increased, while P62 and E-cadherin were decreased in response to NRG2 depletion. The findings of the present study demonstrated that NRG2 acts as a tumor suppressor factor that contributes to the immune escape and anti-tumor immunity inhibition by regulating the pathological process of autophagy and EMT, suggesting that NRG2 could be used as a prognostic biomarker and clinical target for BRCA therapy.