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
{"title":"肺肉瘤样癌的基因组和转录组综合分析确定了与不同免疫特征和临床结果相关的分子亚型","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","doi":"10.1002/cai2.112","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In total, 27 canonical cancer gene mutations were identified, with <i>TP53</i> the most frequently mutated gene, followed by <i>KRAS</i>. Interestingly, most <i>TP53</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"3 3","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.112","citationCount":"0","resultStr":"{\"title\":\"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\",\"doi\":\"10.1002/cai2.112\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In total, 27 canonical cancer gene mutations were identified, with <i>TP53</i> the most frequently mutated gene, followed by <i>KRAS</i>. Interestingly, most <i>TP53</i> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":100212,\"journal\":{\"name\":\"Cancer Innovation\",\"volume\":\"3 3\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.112\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Innovation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cai2.112\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Innovation","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cai2.112","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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 TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 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.
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.