Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes
- Sahil Seth 1,2,3, Runzhe Chen 1,4, Yang Liu 1, Junya Fujimoto 5, Lingzhi Hong 4, Alexandre Reuben 4, Susan Varghese 4, Carmen Behrens 4, Tina McDowell 5,6, Luisa Solis Soto 5, Cara Haymaker 5, Annikka Weissferdt 7, Neda Kalhor 7, Jia Wu 8, Xiuning Le 4, Natalie I Vokes 1,4, Chao Cheng 9, John V Heymach 4, Don L Gibbons 4, P Andrew Futreal 1, Ignacio I Wistuba 5, Humam Kadara 5, Jianhua Zhang 1, Cesar Moran 7, Jianjun Zhang 1,4
- Sahil Seth 1,2,3, Runzhe Chen 1,4, Yang Liu 1
- 1Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 2TRACTION The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 3Graduate School of Biomedical Sciences The University of Texas MD Anderson and the University of Texas Health Science Center Houston Texas USA.
- 4Department of Thoracic/Head and Neck Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 5Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 6Department of Epidemiology The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 7Department of Pathology The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 8Department of Imaging Physics The University of Texas MD Anderson Cancer Center Houston Texas USA.
- 9Department of Medicine Baylor College of Medicine Houston Texas USA.
- 0Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA.
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View abstract on PubMed
Summary
This summary is machine-generated.Pulmonary sarcomatoid carcinoma (PSC) is a rare lung cancer. This study identified two molecular subtypes, with the Immune High subtype showing better survival, emphasizing the role of immune infiltration.
Area Of Science
- Oncology
- Genomics
- Immunology
Background
- Pulmonary sarcomatoid carcinoma (PSC) is a rare, aggressive non-small cell lung cancer (NSCLC) subtype.
- PSC is characterized by both epithelial and sarcoma-like components.
- The molecular and immune landscape of PSC remains poorly understood.
Purpose Of The Study
- To define the molecular and immune landscape of pulmonary sarcomatoid carcinoma.
- To identify subgroups within PSC based on genomic and immunogenic features.
- To correlate these features with clinical outcomes.
Main Methods
- Multiomics profiling including DNA sequencing (panel and whole-exome) and RNA sequencing.
- Analysis of 21 pairs of PSCs and matched normal lung tissues.
- Identification of canonical cancer gene mutations and assessment of immune infiltration.
Main Results
- Identified 27 canonical cancer gene mutations, with TP53 and KRAS being the most frequent.
- Discovered two distinct molecular subtypes of PSC, primarily driven by immune infiltration and signaling.
- The Immune High (IM-H) subtype demonstrated superior survival outcomes.
Conclusions
- Detailed insights into the mutational landscape of PSC were provided.
- Two molecular subtypes of PSC associated with prognosis were identified.
- Tumor immune infiltration significantly impacts the biological and clinical features of PSC, particularly in the IM-H subtype with favorable recurrence-free and overall survival.
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