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Updated: Dec 7, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma
Zhenlin Yang1, Jiachen Xu2, Lin Li3
1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
Abstract:
Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.
Insights
This study reveals the molecular landscape of pulmonary sarcomatoid carcinoma (PSC), a rare lung cancer. Findings identify distinct subgroups and highlight epithelial-mesenchymal transition (EMT) as key, offering new therapeutic strategies for PSC.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Pulmonary sarcomatoid carcinoma (PSC) is a rare lung cancer subtype with a poor prognosis.
- Understanding the molecular underpinnings of PSC is crucial for developing effective treatments.
Purpose of the Study:
- To perform a multi-omics analysis of PSC to elucidate its molecular characteristics.
- To investigate intratumoral heterogeneity and identify key drivers of PSC carcinogenesis.
- To classify PSC into molecular subgroups for targeted therapeutic strategies.
Main Methods:
- Multi-omics analysis of 56 PSC samples, including microdissection of 14 samples for intratumoral heterogeneity analysis.
- Genomic profiling to determine the mutational landscape.
- Pan-cancer analysis and integrated molecular classification.
Main Results:
- Identified shared genomic alterations between epithelial and sarcomatoid components, suggesting a common progenitor.
- Highlighted the significant role of epithelial-mesenchymal transition (EMT) in PSC development.
- Revealed high tumor mutation burden and leukocyte fraction in PSC.
- Classified PSC into three distinct molecular subgroups (C1, C2, C3) with different prognoses and immune microenvironments.
- Found actionable mutations enriched in C1 and C2, while C3 showed longer overall survival and T-cell inflamed microenvironments.
Conclusions:
- The study provides a comprehensive molecular characterization of PSC.
- Identified three distinct PSC subgroups with unique biological features and therapeutic vulnerabilities.
- Findings offer potential entry points for novel treatment strategies for pulmonary sarcomatoid carcinoma.
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