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Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
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Decoding Chemotherapy Resistance of Undifferentiated Pleomorphic Sarcoma at the Single Cell Resolution: A Case

Timur I Fetisov1,2, Maxim E Menyailo1,3, Alexander V Ikonnikov1

  • 1Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), 115093 Moscow, Russia.

Journal of Clinical Medicine
|December 17, 2024
PubMed
Summary

This study reveals chemotherapy resistance mechanisms in undifferentiated pleomorphic sarcoma (UPS) by analyzing single-cell transcriptomes. Identifying gene expression in tumor and microenvironment cells offers potential for personalized UPS treatment strategies.

Keywords:
bioinformaticschemotherapyrecurrenceresistancesingle cell RNA sequencingsoft tissue sarcomatranscriptomeundifferentiated pleomorphic sarcoma

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Area of Science:

  • Oncology
  • Genomics
  • Biotechnology

Background:

  • Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, malignant mesenchymal tumor.
  • Chemotherapy resistance and recurrence are significant challenges in UPS management due to tumor heterogeneity.

Observation:

  • A patient with high-grade UPS developed recurrence after neoadjuvant and adjuvant chemotherapy.
  • Single-cell RNA sequencing was performed on the recurrent UPS sample to analyze cellular composition and gene expression.

Findings:

  • Four tumor cell subpopulations and seven tumor microenvironment (TME) subpopulations were identified.
  • Chemoresistance genes like KLF4, ULK1, LUM, GPNMB, CAVIN1, and AHNAK2 were detected in tumor cells.
  • The TME showed expression of the gemcitabine resistance gene ETS1.

Implications:

  • This research offers the first single-cell transcriptome analysis of chemotherapy-resistant UPS.
  • Identified gene expression patterns in tumor cells and TME may serve as biomarkers for personalized UPS therapy.
  • Understanding these molecular mechanisms could lead to improved treatment strategies for patients with recurrent UPS.