A novel PD-1/PD-L1 pathway molecular typing-related signature for predicting prognosis and the tumor microenvironment in breast cancer

Sep 24, 2026

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Breast cancer immunotherapy targeting the PD-1/PD-L1 pathway advances slowly, and the molecular mechanisms shaping treatment efficacy remain insufficiently defined. Weighted correlation network analysis and negative matrix factorization identify PD-1/PD-L1 pathway-related breast cancer subtypes. Univariate, LASSO, and multivariate Cox models build a prognostic signature and corresponding nomogram. IFNG expression links to the tumor microenvironment and CD8+ T-cell infiltration. The signature stratifies prognosis and supports precision treatment.

LanguageEnglish

CategoryHealthcare

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Pages18

Reading Time45 min

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Introduction

Background and clinical need

PD-1/PD-L1 in tumor immune escape

Rationale for molecular subtyping and signatures

Research A novel PD‑1/PD‑L1 pathway molecular typing‑related signature for predicting prognosis and the tumor microenvironment in breast cancer Yuxin Man1 · Chao Dai2 · Qian Guo1 · Lingxi Jiang2,3 · Yi Shi2,3,4 Received: 11 March 2023 / Accepted: 25 April 2023 © The Author(s) 2023 OPEN Abstract Background Currently, the development of breast cancer immunotherapy based on the PD-1/PD-L1 pathway is relatively slow, and the specific mechanism affecting the immunotherapy efficacy in breast cancer is still unclear. Methods Weighted correlation network analysis (WGCNA) and the negative matrix factorization (NMF) were used to distinguish subtypes related to the PD-1/PD-L1 pathway in breast cancer. Then univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were used to construct the prognostic signature. Anomogram was established based on the signature. The relationship between the signature gene IFNG and breast cancer tumor microenvironment was analyzed. Results Four PD-1/PD-L1 pathway-related subtypes were distinguished. A prognostic signature related to PD-1/PD-L1 pathway typing was constructed to evaluate breast cancer’s clinical characteristics and tumor microenvironment. Thenomogram based on the RiskScore could be used to accurately predict breast cancer patients’ 1-year, 3-year, and 5-year survival probability. The expression of IFNG was positively correlated with CD8+ T cell infiltration in the breast cancer tumor microenvironment. Conclusion A prognostic signature is constructed based on the PD-1/PD-L1 pathway typing in breast cancer, which can guide the precise treatment of breast cancer. The signature gene IFNG is positively related to CD8+ T cell infiltration in breast cancer. Keywords Breast cancer · PD-1 · PD-L1 · Tumor microenvironment · Signature · IFNG Yuxin Man and Chao Dai contributed equally to this work and share the first authorship Supplementary Information The online version contains supplementary material available at [https://doi.org/10.1007/s12672-023-00669-4](https://doi.org/10.1007/s12672-023-00669-4). * Lingxi Jiang, [jlx0128@uestc.edu.cn](jlx0128@uestc.edu.cn); * Yi Shi, [yshi@uestc.edu.cn](yshi@uestc.edu.cn); Yuxin Man, [manyuxin1993@163.com](manyuxin1993@163.com); Chao Dai, [1849325210@qq.com](1849325210@qq.com); Qian Guo, [guoq9014@163.com |](guoq9014@163.com |1Department of Medical Oncology)[1](guoq9014@163.com |1Department of Medical Oncology)[Department of Medical Oncology](guoq9014@163.com |1Department of Medical Oncology), Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China. 2Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China. 3Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China. 4Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan, China. Discover Oncology (2023) 14:59 | [https://doi.org/10.1007/s12672-023-00669-4](https://doi.org/10.1007/s12672-023-00669-4) 1 Introduction As one of the most common cancers worldwide, breast cancer is the leading cause of tumor-related death in women [1]. Currently, treatment strategies for breast cancer are selected based on histopathology and specific genetic characteristics, mainly including surgery, hormone replacement, chemoradiotherapy, and targeted therapy [2, 3] . However, the current effect of conventional treatment is not ideal for patients with advanced breast cancer, especially those with triple-negative breast cance

FAQs

What problem does the study address in breast cancer immunotherapy?

It targets the slow progress of PD-1/PD-L1 pathway immunotherapy in breast cancer and the unclear mechanisms affecting treatment efficacy.

How was the prognostic signature constructed?

WGCNA and NMF distinguished PD-1/PD-L1 pathway-related subtypes, and univariate Cox, LASSO, and multivariate Cox regression were used to build the prognostic signature and risk-score nomogram.

What is the key biological link reported in the results?

The signature gene IFNG shows a positive correlation with CD8+ T-cell infiltration in the breast cancer tumor microenvironment.

Sep 24, 2026

Uploaded by Ezra