Single-cell RNA-seq reveals FGF12 as a prognostic biomarker in low-grade endometrial stromal sarcoma

Front Immunol. 2024 Nov 29:15:1513076. doi: 10.3389/fimmu.2024.1513076. eCollection 2024.

Abstract

Background: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy characterized by its complex tumor microenvironment (TME) and high recurrence rates, posing challenges to accurate prognosis and effective treatment. Identifying prognostic biomarkers is essential for improving patient stratification and guiding therapeutic strategies.

Methods: Using single-cell transcriptome analysis combined with H&E and multiplex immunofluorescence staining, we identified a subpopulation of tumor cells in LG-ESS and further validated the association of this subpopulation and its characteristic genes with LG-ESS prognosis by molecular characterization and bulk transcriptome data.

Results: Our analysis reveals multiple cellular subpopulations within the tumor tissue, particularly a tumor cell subpopulation among them which is associated with poor prognosis. Originating from normal stromal fibroblasts, this subpopulation appears to play a crucial role in TME remodeling, smooth muscle cell behavior, and potentially in tumorigenesis and metastasis. Of particular interest in this subpopulation is the highly expressed FGF12 gene, which is significantly associated with a shortened survival in ESS, highlighting its potential as a prognostic biomarker.

Conclusion: Our study reveals the complexity of TME within the LG-ESS and highlights the role that tumor cell subpopulations play in disease progression and patient prognosis. The identification of FGF12 as a prognostic biomarker suggests a new approach for the personalized treatment and prognosis monitoring of patients.

Keywords: FGF12; low-grade endometrial stromal sarcoma; prognostic biomarker; scRNA-seq; tumor microenvironments.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Endometrial Neoplasms* / diagnosis
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / mortality
  • Endometrial Neoplasms* / pathology
  • Female
  • Fibroblast Growth Factors* / genetics
  • Fibroblast Growth Factors* / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Grading
  • Prognosis
  • RNA-Seq*
  • Sarcoma, Endometrial Stromal* / diagnosis
  • Sarcoma, Endometrial Stromal* / genetics
  • Sarcoma, Endometrial Stromal* / metabolism
  • Sarcoma, Endometrial Stromal* / pathology
  • Single-Cell Analysis*
  • Single-Cell Gene Expression Analysis
  • Transcriptome
  • Tumor Microenvironment* / genetics

Substances

  • Biomarkers, Tumor
  • FGF12 protein, human
  • Fibroblast Growth Factors

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant No. 82060475), National Science and Technology Major Project of National Health Commission of China (Grant No. 2023ZD0502105), Chunhui program of the MOE (Ministry of Education in China) (Grant No. HZKY20220231), MOE Liberal arts and Social Sciences Foundation (Grant No. 24YJCZH462), the Natural Science Foundation of Guizhou Province (Grant No. ZK2022-YB632), Youth Talent Project of Guizhou Provincial Department of Education (Grant No. QJJ2022-224), Excellent Young Talent Cultivation Project of Zunyi City (Zunshi Kehe HZ (2023) 142), Future Journal Pre-proof Science and Technology Elite Talent Cultivation Project of Zunyi Medical University (ZYSE 2023-02), the Key Program of the Education Sciences Planning of Guizhou Province (Grant No.7), Collaborative Innovation Center of MOE (Grant No. 2020-39), Robert Bosch Stiftung (Grant No. 481).