Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review

Abstract

Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood cancers. They exhibit a high tendency to develop early metastases and are often resistant to available treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021 was retrieved from different databases, of which 35 articles were included for analysis. The studies demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the identification of CSC markers in sarcomas may facilitate the development of personalized medicine and improve treatment outcomes.

Keywords: biomarkers; cancer stem cells; drug resistance; sarcomas; systematic review.

Figure 1

Flow diagram illustrating the search process and article screening in different databases that led to the selection of relevant articles for this systematic review.

Figure 2

Number of articles published per year in the last decade on sarcomas, classified as BS, STS, or GIST.

Figure 3

Graphic representation of the articles analyzed in this systematic review. Percentage of articles studying (A) each type of sarcoma; (B) each subtype of BS; (C) each subtype of STS; (D) GIST. Solid colors represent the results of articles in which CSCs were isolated using different techniques and the striped colors represent the results of articles on biomarker expression without isolation of CSCs.

Figure 4

Cell lines and markers used for the study of CSCs in BS: (A) osteosarcoma; (B) Ewing’s sarcoma; (C) chondrosarcoma. Cell lines and markers used for the study of CSCs in STS: (D) synovial sarcoma; (E) rhabdomyosarcoma; (F) fibrosarcoma. (G) Cell lines and markers used for the study of CSCs in GIST.

Figure 5

Representation of the most commonly used CSC markers in samples derived from patients with BS, STS and GIST: (A) CSC isolation; (B) histological techniques.

Figure 6

Number of articles that investigated CSC markers in cell lines after the CSC isolation process, in cell lines without CSC isolation, in patient samples after CSC isolation, and in patient samples without CSC isolation for different STS subtypes: (A) osteosarcoma; (B) chondrosarcoma; and (C) Ewing’s sarcoma; (D) fibrosarcoma; (E) synovial sarcoma; (F) rhabdomyosarcoma; (G) liposarcoma; (H) epithelioid sarcoma and malignant fibrous histiocytoma; (I) leiomyosarcoma; and (J) clear cell sarcoma, alveolar sarcoma, and schwannoma.