Seth Sahil, Chen Runzhe, Liu Yang, Fujimoto Junya, Hong Lingzhi, Reuben Alexandre, Varghese Susan, Behrens Carmen, McDowell Tina, Soto Luisa Solis, Haymaker Cara, Weissferdt Annikka, Kalhor Neda, Wu Jia, Le Xiuning, Vokes Natalie I, Cheng Chao, Heymach John V, Gibbons Don L, Futreal P Andrew, Wistuba Ignacio I, Kadara Humam, Zhang Jianhua, Moran Cesar, Zhang Jianjun
Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA.
TRACTION The University of Texas MD Anderson Cancer Center Houston Texas USA.
Cancer Innov. 2024 Apr 15;3(3):e112. doi: 10.1002/cai2.112. eCollection 2024 Jun.
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.
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.
In total, 27 canonical cancer gene mutations were identified, with the most frequently mutated gene, followed by . Interestingly, most and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.
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.
肺肉瘤样癌（PSC）是一种罕见且侵袭性强的非小细胞肺癌（NSCLC）亚型，其特征是存在上皮和肉瘤样成分。PSC的分子和免疫格局尚未明确界定。
通过靶向高深度DNA panel、全外显子组和RNA测序，对21对PSC及其匹配的正常肺组织进行多组学分析。我们描述了分子和免疫特征，这些特征定义了具有不同基因组和免疫原性特征以及不同临床结局的PSC亚组。
总共鉴定出27种典型癌症基因突变，其中最常发生突变的基因是 ，其次是 。有趣的是，大多数 和KRAS突变是映射到肿瘤主干的早期基因组事件，表明大多数PSC肿瘤存在分支进化。我们鉴定出PSC的两种不同分子亚型，主要由免疫浸润和信号传导驱动。免疫高（IM-H）亚型与较好的生存率相关，突出了免疫浸润对局限性PSC生物学和临床特征的影响。
我们深入了解了PSC的突变格局，并鉴定出两种与预后相关的分子亚型。IM-H肿瘤与良好的无复发生存率和总生存率相关，突出了肿瘤免疫浸润在PSC生物学和临床特征中的重要性。
