EMP3 Expression in HER2-Enriched Breast Cancer is Linked to PI3K/AKT Signaling and Indicates Poor Prognosis

Sep 22, 2026

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EMP3 expression is closely tied to HER2 biology and trastuzumab resistance, yet its prognostic significance in the HER2-enriched subtype remains unclear. This study quantifies EMP3 by immunohistochemistry, tests associations with clinicopathologic features, and applies Cox regression with a nomogram to predict disease-free survival. Genes correlated with EMP3 are identified using R and mapped to PI3K–AKT signaling via KEGG. Functional assays and nude mouse xenografts confirm that EMP3 promotes PI3K/AKT activation and trastuzumab resistance, linking high EMP3 levels to poor outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

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Background

Abstract

Methods

Results

Conclusions

Genetics Research RESEARCH ARTICLE OPEN ACCESS EMP3 Expression in HER2-Enriched Breast Cancer is Linked to PI3K/AKT Signaling and Indicates Poor Prognosis Mingda Zhu1 | Chenyang Tian2 | Ninine Marthe Nkenfag3 | Niannian Wang1 | Weiping Yu1 1Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China | 2Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China | 3Department of Breast, Afliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China Correspondence: Niannian Wang ([898553259@qq.com](898553259@qq.com)) | Weiping Yu ([ywpdoc@126.com](ywpdoc@126.com)) Received: 7 January 2026 | Revised: 10 March 2026 | Accepted: 16 March 2026 Academic Editor: Yaying Sun Keywords: EMP3 | HER2-enriched breast cancer | PI3K–AKT | poor outcomes ABSTRACT Purpose: EMP3 is closely associated with HER2 expression and trastuzumab resistance. However, the prognostic value of EMP3 in the HER2 subtype remains poorly understood. It is necessary to clarify the relationship between EMP3 and prognosis in HER2-enriched breast cancer. Methods: The expression of EMP3 was measured using immunohistochemistry staining. Then, Chi-square tests were carried out to investigate the relationship between EMP3 and relevant clinical data. After that, univariable and multivariable Cox regression were used to flter out factors with independent prognostic value, while a nomogram was constructed to forecast the disease-free survival (DFS) rates of patients. Subsequently, we employed R to identify genes exhibiting a correlation coefcient exceeding 0.6 with EMP3 expression and then mapped such genes onto the PI3K–AKT pathway through the KEGG database. Patients were then stratifed into two subgroups based on the median EMP3 expression, and diferential expression status of the PI3K–AKT pathway between the groups was analyzed. The proliferation capacity under trastuzumab treatment was detected through plate colony formation and EdU incorporation assays in cells with diferent EMP3 expression levels. Nude mouse xenograft tumor formation experiments were employed to further verify the connection between EMP3 expression and trastuzumab resistance. Results: A total of 90 HER2-enriched breast cancer patients were enrolled in this research. EMP3 expression did not exhibit any signifcant association with age, menopausal status, T-stage, N-stage, androgen receptor, Ki67, EGFR, or CK5/6 . Results from univariate and multivariate Cox regression analysis confrmed that EMP3 expression, T-stage, and N-stage served as independent prognostic factors for DFS. The prognostic model constructed based on EMP3 expression, T-stage, and N-stage has good predictive power. The model’s C-index was measured tobe 0.745. The calibration curves ofthe model largely coincided with the diagonal line, suggesting that the actual DFS of patients was almost the same as the DFS predicted by the model. The genes positively associated with EMP3 expression status bear a close association with the PI3K–AKT pathway among HER2-enriched breast cancers. Enhanced activation of the PI3K–AKT pathway was detected in the EMP3 high-expression group. Results derived from both in vitro and in vivo experiments demonstrate that EMP3 regulates the PI3K/AKT pathway and promotes resistance to trastuzumab. Conclusions: High EMP3 expression in HER2-enriched breast cancer predicts poor patient outcomes. Overexpression of EMP3 exerts an upregulatory efect on the PI3K–AKT pathway and boosts the development of trastuzumab resistance. | Mingda Zhu and Chenyang Tian devoted eforts of equal value to the completion of this project. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original wo

FAQs

What question does the study address about EMP3 in HER2-enriched breast cancer?

It investigates the prognostic value of EMP3 specifically in the HER2-enriched subtype and clarifies how EMP3 relates to clinical outcomes.

How was EMP3 expression measured and linked to patient prognosis?

EMP3 expression was assessed using immunohistochemistry staining, then associations with clinical data were tested using chi-square analysis, followed by univariable and multivariable Cox regression and a prognostic nomogram for disease-free survival.

What relationship does the study find between EMP3 and PI3K/AKT signaling and trastuzumab response?

Genes positively associated with EMP3 map to the PI3K–AKT pathway, with enhanced PI3K/AKT activation in the EMP3 high-expression group. In vitro and in vivo experiments show EMP3 regulates PI3K/AKT signaling and promotes resistance to trastuzumab.

Sep 22, 2026

Upload by Sarah