Vahid Yaghoubi Naei, James Monkman, Habib Sadeghirad, Ahmed Mehdi, Tony Blick, William Mullally, Ken O'Byrne, Majid Ebrahimi Warkiani, Arutha Kulasinghe
{"title":"非小细胞肺癌肿瘤和基质区的空间蛋白质组学分析确定了与总生存率相关的特征。","authors":"Vahid Yaghoubi Naei, James Monkman, Habib Sadeghirad, Ahmed Mehdi, Tony Blick, William Mullally, Ken O'Byrne, Majid Ebrahimi Warkiani, Arutha Kulasinghe","doi":"10.1002/cti2.1522","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objectives</h3>\n \n <p>Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune-oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Survival analysis revealed that stromal CD56 (HR = 0.384, <i>P</i> = 0.06) and tumoral TIM3 (HR = 0.703, <i>P</i> = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, <i>P</i> = 0.02) and cleaved caspase 9 (HR = 1.575, <i>P</i> = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM-3 (HR = 0.614, <i>P</i> = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, <i>P</i> = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, <i>P</i> = 0.008) was linked to poorer survival in the tumor.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Deciphering the TME using high-plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257771/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spatial proteomic profiling of tumor and stromal compartments in non-small-cell lung cancer identifies signatures associated with overall survival\",\"authors\":\"Vahid Yaghoubi Naei, James Monkman, Habib Sadeghirad, Ahmed Mehdi, Tony Blick, William Mullally, Ken O'Byrne, Majid Ebrahimi Warkiani, Arutha Kulasinghe\",\"doi\":\"10.1002/cti2.1522\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune-oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Survival analysis revealed that stromal CD56 (HR = 0.384, <i>P</i> = 0.06) and tumoral TIM3 (HR = 0.703, <i>P</i> = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, <i>P</i> = 0.02) and cleaved caspase 9 (HR = 1.575, <i>P</i> = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM-3 (HR = 0.614, <i>P</i> = 0.04) on OS. 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Spatial proteomic profiling of tumor and stromal compartments in non-small-cell lung cancer identifies signatures associated with overall survival
Objectives
Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays.
Methods
In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune-oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).
Results
Survival analysis revealed that stromal CD56 (HR = 0.384, P = 0.06) and tumoral TIM3 (HR = 0.703, P = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, P = 0.02) and cleaved caspase 9 (HR = 1.575, P = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM-3 (HR = 0.614, P = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, P = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, P = 0.008) was linked to poorer survival in the tumor.
Conclusions
Deciphering the TME using high-plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.
期刊介绍:
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.