bims-myxlip 2022-01-30 papers

Issue of 2022–01–30
two papers selected by
Laura Mannarino, Humanitas Research

Int J Mol Med. 2022 Mar;pii: 39. [Epub ahead of print]49(3):

Splice variants denote differences between a cancer stem cell side population of EWSR1‑ERG‑based Ewing sarcoma cells, its main population and EWSR1‑FLI‑based cells.

Eberhard Korsching, Julian Matschke, Marc Hotfilder.

Ewing sarcoma is a challenging cancer entity, which, besides the characteristic presence of a fusion gene, is driven by multiple alternative splicing events. So far, splice variants in Ewing sarcoma cells were mainly analyzed for EWSR1‑FLI1. The present study provided a comprehensive alternative splicing study on CADO‑ES1, an Ewing model cell line for an EWSR1‑ERG fusion gene. Based on a well‑-characterized RNA‑sequencing dataset with extensive control mechanisms across all levels of analysis, the differential spliced genes in Ewing cancer stem cells were ATP13A3 and EPB41, while the main population was defined by ACADVL, NOP58 and TSPAN3. All alternatively spliced genes were further characterized by their Gene Ontology (GO) terms and by their membership in known protein complexes. These results confirm and extend previous studies towards a systematic whole‑transcriptome analysis. A highlight is the striking segregation of GO terms associated with five basic splice events. This mechanistic insight, together with a coherent integration of all observations with prior knowledge, indicates that EWSR1‑ERG is truly a close twin to EWSR1‑FLI1, but still exhibits certain individuality. Thus, the present study provided a measure of variability in Ewing sarcoma, whose understanding is essential both for clinical procedures and basic mechanistic insight.

Keywords: CADO‑ES1; EWSR1‑ERG; Ewing sarcoma; alternative splicing; cancer stem cell; rMATS

DOI: https://doi.org/10.3892/ijmm.2022.5094

Ann Transl Med. 2021 Dec;9(24): 1764

Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis.

Jingyi Dang, Jun Fu, Zhao Zhang, Dong Liu, Debin Cheng, Hongbin Fan.

Background: This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).
Methods: Multiple databases, including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure, were searched to retrieve relevant articles. Ultimately, the full text of 10 studies involving the use of trabectedin and doxorubicin in STS were reviewed. Review Manager 5.2 was used to evaluate the heterogeneity of the results of the selected articles. Forest plot, bias, and sensitivity analyses were carried out on the included articles.
Results: Ten papers that met the criteria were included in this analysis. STS patients receiving trabectedin had longer progression-free survival than those receiving doxorubicin [overall mean difference (MD) =1.36, 95% confidence interval (CI): 1.04, 1.68, I2=6%, fixed-effects model]. The experimental group also had a longer overall survival period than the control group (MD =3.92, 95% CI: 0.23, 7.60, P=0.04 and I2=83%, random-effects model), and the experimental group had a better disease control rate than the control group (relative risk =1.2, P=0.03 and I2=45%, fixed-effects model). From the publication bias analysis and sensitivity analysis, we can guarantee the results are robust and unbiased.
Discussion: Our research showed that STS patients who received trabectedin had better clinical effects and a longer survival time than those who received doxorubicin.

Keywords: Trabectedin; doxorubicin; meta-analysis; soft tissue sarcoma (STS)

DOI: https://doi.org/10.21037/atm-21-6033