Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer

Sep 23, 2026

Endometrial cancer shows rising incidence and mortality, yet biomarkers and predictive methods for immunotherapy response and patient prognosis remain insufficient. This study integrates multiple programmed cell death (PCD) pathways with multi-omics data from TCGA-EC and GEO to define two endometrial cancer subgroups with distinct survival, tumor microenvironment profiles, and immunotherapy responses. Single-cell RNA sequencing clarifies PCD-related tumor heterogeneity and yields seven key genes forming a prognostic risk score. Lower risk predicts better survival and stronger immunotherapy benefit; higher risk indicates poor outcomes and reduced efficacy, with potential value for alternative therapies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Identification of PCD-based endometrial cancer subgroups

PCD pathways and biological background

Multi-omics integration and immunotherapy response analysis

Single-cell RNA sequencing and tumor heterogeneity

Gene signature and prognostic risk scoring

Clinical implications for survival and therapy selection

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer Shan Lu1,2,8, Yiyun Wei1,8, Liuyan Chen3,8, Jinlian Cheng1, Liuyan Qin1, Xuemei Lu4 & Lihong Pang1,5,6,7􀀍 Endometrial cancer (EC) is one of the few malignancies with increasing incidence and mortality rates. Targeted therapy and immunotherapy have become pivotal treatment strategies for EC patients. However, the current methods and biomarkers for predicting immunotherapy responses and prognosis are remain limited. Programmed cell death (PCD) pathways play a crucial role in cancer development and progression and may serve as prognostic markers and indicators of drug sensitivity in EC. In our study, we integrated multiple PCD pathways and comprehensive multi-omics datasets from TCGA-EC and GEO databases. By analyzing distinct PCD signatures, we discovered two major EC subgroups with distinctive prognoses, tumor microenvironment (TME) profiles, and responses to immunotherapy. To further investigate the cellular basis of these PCD patterns, single-cell RNA sequencing analysis was conducted to explore tumor heterogeneity in PCD characteristics across EC subpopulations. Further investigation revealed seven key PCD-associated genes (HIF3A, ACTL8, SIRPG, FBN3, ARHGAP30, CD6, and P2RY13) that formed the basis for a novel prognostic scoring system—risk score (RS) . Our findings showed that patients with lower risk scores had better survival rates and improved immunotherapy outcomes. Conversely, patients with higher risk scores experienced poor clinical outcomes and reduced immunotherapy efficacy, although alternative therapies such as docetaxel andolaparib demonstrated potential therapeutic benefits. Overall, the RS provides a valuable tool for early prognosis prediction and for identifying patients who may benefit from immunotherapy. Keywords Bioinformatics, Endometrial Cancer, Immunotherapy, Prognosis Among female malignancies globally, endometrial cancer (EC) ranks as the sixth most common cancer and the second most frequent gynecologic malignancy, with an estimated 417,000 cases worldwide in 2020. Over the past three decades, the incidence of this disease has increased dramatically by 132%1,2. While early detection is achieved in approximately 90% of cases, leading to favorable 5-year survival outcomes through surgical intervention alone or in combination with localized treatments, patients experiencing recurrence face significant challenges due to uncertainties surrounding the optimal adjuvant therapeutic strategies3,4. This clinical scenario highlights the urgent need for reliable predictive models for both survival outcomes and immunotherapy efficacy, enabling more personalized treatment approaches. 1Department of Prenatal Diagnosis and Genetic Disease Diagnosis, The FirstAffliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. 2Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China. 3Key Laboratory of Biological Molecular Medicine Research (Guangxi Medical University), Education Department of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China. 4Guangxi Medical University Nursing College, Nanning, Guangxi, China. 5NHC Key Laboratory of Thalassemia Medicine (Guangxi Medical University), Nanning, Guangxi, China. 6Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China. 7Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, China. 8Shan Lu, Yiyun Wei and Liuyan Chen contributed equally to this work. 􀀍 email: [673869247@qq.com](673869247@qq.com) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Programmed cell death (PCD) is

FAQs

What clinical problem does the study address in endometrial cancer?

It addresses the limited ability to predict immunotherapy response and prognosis in endometrial cancer using current biomarkers and predictive methods.

How were programmed cell death patterns used in the analysis?

The study integrated multiple PCD pathways with multi-omics datasets to identify distinct PCD signatures and two major endometrial cancer subgroups with different outcomes and tumor microenvironment profiles.

What is the prognostic risk score (RS) based on?

The RS is built from seven key PCD-associated genes identified through investigation, and it separates patients into lower- and higher-risk groups.

How does RS relate to immunotherapy effectiveness and survival?

Patients with lower RS showed better survival and improved immunotherapy outcomes, while higher RS correlated with poor clinical outcomes and reduced immunotherapy efficacy. The study also notes possible benefits from alternative therapies such as docetaxel and olaparib.

Sep 23, 2026

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