Integrative Genomic and Transcriptomic Profiling of Pulmonary Sarcomatoid Carcinoma Identifies Molecular Subtypes Associated With Distinct Immune Features and Clinical Outcomes

Authors

Sahil Seth
Runzhe Chen
Yang Liu
Junya Fujimoto
Lingzhi Hong
Alexandre Reuben
Susan Varghese
Carmen Behrens
Tina McDowell
Luisa Solis Soto
Cara Haymaker
Annikka Weissferdt
Neda Kalhor
Jia Wu
Xiuning Le
Natalie I Vokes
Chao Cheng
John V Heymach
Don L Gibbons
P Andrew Futreal
Ignacio I Wistuba
Humam Kadara
Jianhua Zhang
Cesar Moran
Jianjun Zhang

Publication Date

6-1-2024

Journal

Cancer Innovation

Abstract

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined.

METHODS: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.

RESULTS: In total, 27 canonical cancer gene mutations were identified, with

CONCLUSIONS: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

Keywords

genomic, immune, pulmonary sarcomatoid carcinoma, survival

Comments

Supplementary Material

PMID: 38947760

DOI

10.1002/cai2.112

PMID

38947760

PMCID

PMC11212327

PubMedCentral® Posted Date

April 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes