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

Zhou,Ruijie; Zhou,Ruijie; Dai,Jinjin; Dai,Jinjin; Zhou,Runlong; Zhou,Runlong; Wang,Mengyi; Wang,Mengyi; Deng,Xiaotong; Deng,Xiaotong; Zhuo,Qing; Zhuo,Qing; Wang,Zhenrong; Wang,Zhenrong; Li,Fan; Li,Fan; Yao,Di; Yao,Di; Xu,Yao; Xu,Yao

doi:10.3892/ol.2024.14410

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

Authors:
- Ruijie Zhou
- Jinjin Dai
- Runlong Zhou
- Mengyi Wang
- Xiaotong Deng
- Qing Zhuo
- Zhenrong Wang
- Fan Li
- Di Yao
- Yao Xu
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Affiliations: Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China, Wuhan Bio‑Raid Biotechnology Co., Ltd., Wuhan, Hubei 430075, P.R. China
Published online on: April 23, 2024 https://doi.org/10.3892/ol.2024.14410
Article Number: 277
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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