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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1560625
Single-cell sequencing reveals the role of aggrephagy-related patterns in tumor microenvironment, prognosis and immunotherapy in endometrial cancer
Provisionally accepted
Yuquan Yuan 1 Chunyan Ren 1 Jin Shu 2 Keyang Zhu 3 Ganghui Li 1 Bao Liu 1 Jianrong Huang 1
Yinde Huang 4
Chengzhi Zhao 1*- 1 Chongqing Health Center for Women and Children, Chongqing, China
- 2 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Cancer Hospital, Chongqing University, Chongqing, China
- 3 North Sichuan Medical College, Nanchong, Sichuan Province, China
- 4 Chongqing General Hospital, Chongqing, Chongqing, China
Background: As a type of autophagy, aggrephagy degrades the aggregation of misfolded protein in cells and plays an important role in key genetic events for various cancers. However, aggrephagy functions within the tumor microenvironment (TME) in endometrial cancer (EC) remain to be elucidated.Methods: A total of 36,227 single cells from single-cell RNA-seq data derived from five EC tumor samples were comprehensively analyzed using a nonnegative matrix factorization (NMF) algorithm for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from public repositories were utilized to assess the prognostic value of aggrephagyrelated TME clusters and predict immune checkpoint blockade immunotherapeutic response in EC.Results: Fibroblasts, macrophages, CD8+T cells, and lymphatic endothelial cells were categorized into two to five aggrephagy-related subclusters, respectively. CellChat analysis showed that the aggrephagy-related subtypes of TME cells exhibited extensive interactions with tumor epithelial cells, particularly for macrophages. Moreover, aggrephagy regulators may be significantly associated with the pseudotime trajectories of major TME cell types as well as the clinical and biological features of EC. Bulk-seq analysis showed that these aggrephagy-related subclusters had significant predictive value for the survival and immune checkpoint blockade response in EC patients.Notably, immunohistochemical staining results manifested that the TUBA1A+ macrophage subtype was linked to less lymph node metastasis and longer survival, which were consistent with the bioinformatics analysis findings.Conclusions: This study provided a novel view of aggrephagy signaling in the EC tumor microenvironment, and intervention of aggrephagy was expected to improve the survival rate of EC patients.
Keywords: endometrial cancer, Aggrephagy, Tumor Microenvironment, Immunohistochemistry, prognosis
Received: 15 Jan 2025; Accepted: 04 Mar 2025.
Copyright: © 2025 Yuan, Ren, Shu, Zhu, Li, Liu, Huang, Huang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chengzhi Zhao, Chongqing Health Center for Women and Children, Chongqing, China
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