Fetisov Timur I, Menyailo Maxim E, Ikonnikov Alexander V, Khozyainova Anna A, Tararykova Anastasia A, Kopantseva Elena E, Korobeynikova Anastasia A, Senchenko Maria A, Bokova Ustinia A, Kirsanov Kirill I, Yakubovskaya Marianna G, Denisov Evgeny V
Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), 115093 Moscow, Russia.
N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia.
J Clin Med. 2024 Nov 26;13(23):7176. doi: 10.3390/jcm13237176.
Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we characterized the cell composition and the transcriptional profile of UPS with resistance to chemotherapy at the single cell resolution. A 58-year-old woman was diagnosed with a 13.6 × 9.3 × 6.0 cm multi-nodular tumor with heterogeneous cysto-solid structure at the level of the distal metadiaphysis of the left thigh during magnetic resonance tomography. Morphological and immunohistochemical analysis led to the diagnosis of high-grade (G3) UPS. Neoadjuvant chemotherapy, surgery (negative resection margins), and adjuvant chemotherapy were conducted, but tumor recurrence developed. The UPS sample was used to perform single-cell RNA sequencing by chromium-fixed RNA profiling. Four subpopulations of tumor cells and seven subpopulations of tumor microenvironment (TME) have been identified in UPS. The expression of chemoresistance genes has been detected, including (doxorubicin and ifosfamide), , , , and (doxorubicin), and (gemcitabine) in tumor cells and (gemcitabine) in TME. This study provides the first description of the single-cell transcriptome of UPS with resistance to two lines of chemotherapy, showcasing the gene expression in subpopulations of tumor cells and TME, which may be potential markers for personalized cancer therapy.
未分化多形性肉瘤（UPS）是一种高度恶性的间充质肿瘤，是最常见的软组织肉瘤类型之一。尽管化疗可提高UPS患者的5年生存率，但高度的肿瘤异质性常常导致化疗耐药，进而导致肿瘤复发。在本研究中，我们在单细胞分辨率水平上对具有化疗耐药性的UPS的细胞组成和转录谱进行了表征。一名58岁女性在磁共振断层扫描时，于左大腿远端干骺端水平被诊断出患有一个13.6×9.3×6.0 cm的多结节肿瘤，具有异质性囊实性结构。形态学和免疫组化分析确诊为高级别（G3）UPS。患者接受了新辅助化疗、手术（切缘阴性）和辅助化疗，但仍出现了肿瘤复发。利用该UPS样本通过铬固定RNA分析进行单细胞RNA测序。在UPS中鉴定出了四个肿瘤细胞亚群和七个肿瘤微环境（TME）亚群。检测到了化疗耐药基因的表达，包括肿瘤细胞中的（阿霉素和异环磷酰胺）、、、、和（阿霉素），以及TME中的（吉西他滨）和（吉西他滨）。本研究首次描述了对两线化疗耐药的UPS的单细胞转录组，展示了肿瘤细胞亚群和TME中的基因表达情况，这些可能是个性化癌症治疗的潜在标志物。
