Characterization of transcriptional heterogeneity and novel therapeutic targets using single cell RNA-sequencing of primary and circulating Ewing sarcoma cells.
Andrew E GoodspeedAvery BodlakAlexis B DuffySarah Nelson-TaylorNaoki OikeTimothy PorfilioRyota ShiraiDeandra WalkerAmy TreeceJennifer O BlackNathan DonaldsonCarrye CostTim GarringtonBrian GreffeSandra Luna-FinemanJenna M SopfeJessica A LakeEtienne DanisMichael R VernerisDaniel L AdamsMasanori HayashiPublished in: bioRxiv : the preprint server for biology (2024)
Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.
Keyphrases
- single cell
- gene expression
- rna seq
- copy number
- circulating tumor cells
- transcription factor
- high throughput
- papillary thyroid
- mitochondrial dna
- genome wide
- end stage renal disease
- dna methylation
- squamous cell
- chronic kidney disease
- squamous cell carcinoma
- newly diagnosed
- ejection fraction
- induced apoptosis
- small cell lung cancer
- young adults
- childhood cancer
- signaling pathway
- peritoneal dialysis
- heat shock
- oxidative stress
- soft tissue
- circulating tumor
- patient reported
- free survival
- combination therapy
- data analysis