Integrated Molecular Characterization Reveals Potential Therapeutic Strategies for Pulmonary Sarcomatoid Carcinoma

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Sep 28

PMID 32985499

Citations 32

Authors

Zhenlin Yang

Jiachen Xu

Lin Li

Renda Li

Yalong Wang

Yanhua Tian

Wei Guo

Zhijie Wang

Fengwei Tan

Jianming Ying

Yuchen Jiao

Shugeng Gao

Jie Wang

Yibo Gao

Jie He

Affiliations

Soon will be listed here.

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.

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