Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes.

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.

Informations de copyright

© 2024 The Authors. Cancer Innovation published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.

Déclaration de conflit d'intérêts

Ignacio I. Wistuba reports consulting or advisory roles for AstraZeneca/MedImmune, Bayer, Bristol‐Myers Squibb, Genentech/Roche, GlaxoSmithKline, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Jansen, Novartis, Flame Inc, and Pfizer; has received grants and personal fees from Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, HTG Molecular, Merck, and Guardant Health; has received personal fees from GlaxoSmithKline and Oncocyte, Daiichi‐Sankyo, Roche, Astra Zeneca, Pfizer, and Bayer; has received research funding to his institution from 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Iovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novartis, OncoPlex Diagnostics, Pfizer, Takeda, and Novartis. Jianjun Zhang reports research funding from Merck, Johnson and Johnson, and consultant fees from BMS, Johnson and Johnson, AstraZeneca, Geneplus, OrigMed, and Innovent outside the submitted work. John V. Heymach reports honorariums from AstraZeneca, Boehringer‐Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Guardant Health, Foundation Medicine, Hengrui Therapeutics, Eli Lilly, Novartis, Spectrum, EMD Serono, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, EMD Serono, Pneuma Respiratory, Kairos Venture Investments, Roche and Leads Biolabs. Runzhe Chen reports stock options from BeiGene outside the submitted work. Cara Haymaker received funding to institution from Avenge Bio, Sanofi, Dragonfly, BTG, Iovance Biotherapeutics, KSQ, Obsidian and Virogen, personal fees from Regeneron and stock options from BriaCell as a member of the scientific advisory board outside the submitted work. Alexandre Reuben serves on the Scientific Advisory Board and has received honoraria from Adaptive Biotechnologies. Natalie I Vokes reports consulting roles for Sanofi, Oncocyte, Lilly, Regeneron, Amgen, Xencor, Astra Zeneca, Tempus and Pfizer, and travel reimbursement from regeneron. Professor Jianjun Zhang is a member of the Cancer Innovation Editorial Board. To minimize bias, he was excluded from all editorial decision‐making related to the acceptance of this article for publication. The remaining authors declare no conflict of interest.