Related Experiment Video
Updated: May 19, 2026
06:13
Colony Formation Assay Detecting the Proliferative Capacity of LncRNA-knockdown Osteosarcoma Cells
Published on: January 16, 2026
Paired single cell analysis reveals chemotherapy resistance in osteosarcoma
Li Hu1,2, Yaxin Zhang1,2, Boyang Wang3,2
1Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China.
Cancer Drug Resistance (Alhambra, Calif.)
|May 18, 2026
Summary
This study identified a nine-gene signature predicting osteosarcoma chemotherapy resistance and poor outcomes. Targeting PI3K with Pictilisib shows promise for refractory osteosarcoma patients.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Osteosarcoma is an aggressive bone cancer with poor prognosis, especially in chemotherapy-resistant cases.
- Existing treatments often face challenges due to resistance, necessitating novel therapeutic strategies.
Purpose of the Study:
- To characterize the transcriptional landscape of chemotherapy-resistant osteosarcoma cells.
- To develop a prognostic gene signature for predicting treatment response.
- To identify potential therapeutic vulnerabilities in resistant osteosarcoma.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) on paired pre- and post-neoadjuvant chemotherapy (NAC) osteosarcoma specimens.
- Pseudotime analysis to reconstruct resistance trajectories.
- Validation of a nine-gene resistance signature in independent bulk RNA-seq cohorts (PKPH and TARGET).
- Drug sensitivity prediction using oncoPredict.
Main Results:
- Chemotherapy induced a stromal-dominant, immune-sparse niche and expansion of non-tumor cells.
- A nine-gene module (KCNMA1, KIF21A, MIR181A1HG, RPS27, PDPN, ADIRF, PRELP, PHEX, COL9A2) was upregulated in resistant cells.
- The nine-gene signature correlated with poorer histopathologic response and shorter progression-free survival.
- Pictilisib, a PI3K inhibitor, showed predicted efficacy in high-resistance score subsets.
Conclusions:
- A nine-gene signature effectively links pre-treatment tumor biology to NAC response and patient outcomes.
- PI3K pathway inhibition represents a promising therapeutic strategy for refractory osteosarcoma.
- Paired scRNA-seq analysis provides a powerful tool for understanding treatment resistance in cancer.
