Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma.
Zhenlin YangJiachen XuLin LiRenda LiYalong WangYanhua TianWei GuoZhijie WangFengwei TanJianming YingYucheng JiaoShugeng GaoJie WangYibo GaoJie HePublished in: Nature communications (2020)
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.
Keyphrases
- poor prognosis
- epithelial mesenchymal transition
- single cell
- long non coding rna
- pulmonary hypertension
- end stage renal disease
- ejection fraction
- chronic kidney disease
- transforming growth factor
- signaling pathway
- single molecule
- prognostic factors
- papillary thyroid
- risk assessment
- copy number
- patient reported outcomes
- climate change
- risk factors
- young adults
- patient reported
- genome wide
- squamous cell
- free survival
- smoking cessation