High-dimensional deconstruction of ovarian cancer at single-cell precision reveals HEBP2 that reshape the TIME and drive carboplatin resistance - Translational Oncology 44 - Article 101917

Sep 21, 2026

Single-cell sequencing was used to profile the tumor immune microenvironment in ovarian cancer patients and to examine how evolutionary macrophage subgroups contribute to disease progression and fatty-acid metabolism programs linked to drug resistance. Multiple single-cell RNA-seq datasets were integrated to define mechanisms of ovarian cancer chemoresistance and carboplatin resistance. HEBP2 was shown to promote progression, reshape the immune landscape by polarizing M0_TAM to M2_TAM, reduce chemotherapy efficacy, and enhance proliferation while suppressing apoptosis in resistant models. These findings position HEBP2 as a prognostic marker and therapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Tumor immune microenvironment and drug resistance context

Results

Methods

Conclusion

Translational Oncology 44 (2024) 101917 Contents lists available at ScienceDirect Translational Oncology journal [homepage:](homepage: www.elsevier.com/locate/tranon)[ www.elsevier.com/locate/tranon](homepage: www.elsevier.com/locate/tranon) | Original Research
High-dimensional deconstruction of ovarian cancer at single-cell precision reveals HEBP2 that reshape the TIME and drive carboplatin resistance BiKang Yang , Miao Dai *
Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords: Single-cell Ovarian cancer
Drug resistance HEBP2
Macrophage | | Background: Single-cell sequencing was employed to analyze the tumor immune microenvironment in ovarian cancer (OC) patients, exploring the evolutionary roles of various macrophage subgroups in OC progression and their correlation with fatty acid metabolism-related genes in contributing to drug resistance.
Methods: This study aimed to decipher the mechanisms underlying OC chemoresistance (OC-CR) and carboplatin resistance by integrating and analyzing multiple single-cell RNA sequencing datasets from OC patients. The tumor immune microenvironment in OC-CR patients exhibited notable alterations in cellular interactions and the proportions of different immune cell populations, in contrast to the cohort sensitive to OC chemotherapy. Results: The study demonstrates that the fatty acid-associated gene HEBP2 not only accelerates OC progression but also modifies the immune landscape of OC, driving the polarization from M0_TAM to M2_TAM. This shift results in a diminished efficacy of chemotherapy in OC. Furthermore, both in vitro and in vivo experiments underscored HEBP2′s role in boosting the proliferation of OC-resistant cell lines and suppressing apoptosis, thereby facilitating carboplatin resistance.
Conclusion: In conclusion, the immune microenvironments of OC-CR significantly differ from those sensitive to chemotherapy, underscoring HEBP2′s role in fostering OC resistance. This establishes HEBP2 as a promising prognostic marker and a novel target for therapeutic strategies against OC resistance. | Introduction Ovarian cancer is a highly lethal malignancy within gynecology, characterized by a concerning mortality rate. Recently, its incidence has been rising steadily, garnering increased attention from the medical community [1]. The use of prenatal ultrasonography has uncovered more asymptomatic ovarian masses, around 5 % of which are malignant, affecting cancer incidence. Current practice advises surgical intervention for masses over 6 cm or those showing symptoms [2]. Despite advancements in clinical management through conventional surgery, chemotherapy, radiation, and targeted therapy, these treatments often have limited efficacy due to ovarian cancer’s intricate pathogenesis [3, 4]. This complexity arises from the interplay of various molecular and cellular pathways, complicating both the disease and its treatment. Recent shifts towards systemic therapies underscore the critical role of predictive biomarkers in ovarian cancer management. The evolution from traditional chemotherapy to the integration of targeted treatments has been marked by significant milestones, highlighting the need for ongoing research into the dynamic therapeutic landscape of ovarian cancer. Studies such as the MOUSEION series provide pivotal insights into this arena, demonstrating the influence of gender and performance status on the efficacy of immunotherapies [5,6]. These findings advocate for a personalized approach to treatment, emphasizing the importance of biomarkers in optimizing therapeutic outcomes [7].Consequently, an in-depth understanding of ovarian cancer’s molecular mechanisms and the identification of novel molecular targets are imperative for developing more effective thera

FAQs

How was the ovarian cancer tumor immune microenvironment analyzed in this study?

Single-cell sequencing was used, with integration of multiple single-cell RNA-seq datasets from ovarian cancer patients to profile cellular interactions and immune cell population differences.

What role does HEBP2 play in carboplatin resistance?

HEBP2 is associated with accelerated ovarian cancer progression and immune landscape remodeling, including macrophage polarization that diminishes chemotherapy efficacy; in vitro and in vivo data support its role in boosting resistant cell proliferation and suppressing apoptosis.

What macrophage changes were observed between chemoresistant and chemotherapy-sensitive cohorts?

The study reports a polarization shift from M0_TAM to M2_TAM in the chemoresistant tumor immune microenvironment compared with the sensitive cohort.

Sep 21, 2026

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