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Proteogenomics of n...
Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms
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- Lehtiö, Janne (author)
- Karolinska Institutet,Karolinska Institute
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- Arslan, Taner (author)
- Karolinska Institute
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- Siavelis, Ioannis (author)
- Karolinska Institutet,Karolinska Institute
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- Pan, Yanbo (author)
- Karolinska Institutet,Karolinska Institute
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- Socciarelli, Fabio (author)
- Karolinska Institute
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- Berkovska, Olena (author)
- Karolinska Institutet,Karolinska Institute
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- Umer, Husen M. (author)
- Karolinska Institutet,Karolinska Institute
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- Mermelekas, Georgios (author)
- Karolinska Institute
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- Pirmoradian, Mohammad (author)
- Karolinska Institute
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- Jönsson, Mats (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Region Skåne
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- Brustugun, Odd Terje (author)
- Vestre Viken Health Trust,Oslo university hospital
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- Purohit, Krishna Pinganksha (author)
- University of Edinburgh
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- Cunningham, Richard (author)
- University of Edinburgh
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- Foroughi Asl, Hassan (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Isaksson, Sofi (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Arbajian, Elsa (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Aine, Mattias (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Karlsson, Anna (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Kotevska, Marija (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Gram Hansen, Carsten (author)
- University of Edinburgh
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- Drageset Haakensen, Vilde (author)
- Oslo university hospital
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- Helland, Åslaug (author)
- Oslo university hospital,University of Oslo
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- Tamborero, David (author)
- Karolinska Institutet,Karolinska Institute
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- Johansson, Henrik J. (author)
- Karolinska Institutet,Karolinska Institute
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- Branca, Rui M. (author)
- Karolinska Institutet,Karolinska Institute
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- Planck, Maria (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Staaf, Johan (author)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Orre, Lukas M. (author)
- Karolinska Institutet,Karolinska Institute
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(creator_code:org_t)
- 2021-11-22
- 2021
- English 19 s.
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In: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:11, s. 1224-1242
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lehtiö, Janne
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Arslan, Taner
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Siavelis, Ioanni ...
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Pan, Yanbo
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Socciarelli, Fab ...
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Berkovska, Olena
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show more...
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Umer, Husen M.
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Mermelekas, Geor ...
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Pirmoradian, Moh ...
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Jönsson, Mats
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Brunnström, Hans
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Brustugun, Odd T ...
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Purohit, Krishna ...
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Cunningham, Rich ...
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Foroughi Asl, Ha ...
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Isaksson, Sofi
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Arbajian, Elsa
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Aine, Mattias
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Karlsson, Anna
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Kotevska, Marija
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Gram Hansen, Car ...
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Drageset Haakens ...
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Helland, Åslaug
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Tamborero, David
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Johansson, Henri ...
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Branca, Rui M.
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Planck, Maria
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Staaf, Johan
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Orre, Lukas M.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Nature Cancer
- By the university
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Lund University
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Karolinska Institutet