In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations
Abstract Genomic alterations in tumor cells can influence immune response, as has been demonstrated in several tumor types. For instance, mutations in certain genes like EGFR or B-RAF are associated with a particular immune phenotype. Non-small cell lung cancer (NSCLC) is one of the most immunogenic...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-02494-x |
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| author | Cristina Nieto-Jiménez Esther Garcia-Lorenzo Cristina Diaz-Tejeiro Lucía Paniagua-Herranz Adrián Sanvicente Bernard Doger Irene Moreno Manuel Pedregal Jorge Bartolomé Arancha Manzano Gyöngyi Munkácsy Balázs Győrffy Pedro Pérez-Segura Emiliano Calvo Victor Moreno Alberto Ocana |
| author_facet | Cristina Nieto-Jiménez Esther Garcia-Lorenzo Cristina Diaz-Tejeiro Lucía Paniagua-Herranz Adrián Sanvicente Bernard Doger Irene Moreno Manuel Pedregal Jorge Bartolomé Arancha Manzano Gyöngyi Munkácsy Balázs Győrffy Pedro Pérez-Segura Emiliano Calvo Victor Moreno Alberto Ocana |
| author_sort | Cristina Nieto-Jiménez |
| collection | DOAJ |
| description | Abstract Genomic alterations in tumor cells can influence immune response, as has been demonstrated in several tumor types. For instance, mutations in certain genes like EGFR or B-RAF are associated with a particular immune phenotype. Non-small cell lung cancer (NSCLC) is one of the most immunogenic tumors, but certain genomic alterations can modulate and influence immune response. In the present work, we explore the transcriptomic landscape and immunologic profile of NSCLC with molecular alterations in SMARCA4. Using the TCGA repository we exploited their analysis with R and other available packages. cBioPortal was used to explore and analyze the mutational profile present in those tumors The prognostic value of identified genes in patients treated with immunotherapy was evaluated using the KMplotter online tool, and for correlations with immune populations TIMER 2.0 was interrogated. In lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) disruptive mutations in SMARCA4 were presented in 8%, and 4% of the cases, respectively. Gene deletions were observed in 1% of the population. The transcriptomic profile in LUAD and LUSC with deletions or disruptive mutations was explored. Interrogating TCGA using a 2.5 gene expression fold change (FC) we observed five genes commonly upregulated, and thirty-one genes commonly decreased when SMARCA4 was mutated or CNV loss was present. Enriched biological functions for downregulated genes included “Antigen processing and presentation, endogenous lipid antigen via MHC class Ib. Expression of CD1A, CD1C, CD1E, CX3CR1, and MYO1G showed a strong positive correlation with dendritic cells (DC) and dendritic cells resting (DCR). The increased expression of gene signatures formed by these transcripts resulted in a better prognosis in a set of patients with different tumors treated with anti-PD1 therapies, including 21 non-small cell lung cancers. We evaluated genomic alterations and transcriptomic patterns of SMARCA4 alterations in NSCLC tumors, identifying a relevant immunologic downregulated gene set linked with antigen presentation that predicts response to anti-PD1 therapies. |
| format | Article |
| id | doaj-art-023c5f2c8f4f4a609d8c844f47b4c0b2 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-023c5f2c8f4f4a609d8c844f47b4c0b22025-08-20T02:29:45ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-02494-xIn silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterationsCristina Nieto-Jiménez0Esther Garcia-Lorenzo1Cristina Diaz-Tejeiro2Lucía Paniagua-Herranz3Adrián Sanvicente4Bernard Doger5Irene Moreno6Manuel Pedregal7Jorge Bartolomé8Arancha Manzano9Gyöngyi Munkácsy10Balázs Győrffy11Pedro Pérez-Segura12Emiliano Calvo13Victor Moreno14Alberto Ocana15Experimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de Investigación Sanitaria San Carlos (IdISSC)START Madrid-FJD, Hospital Fundación Jiménez DíazExperimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de Investigación Sanitaria San Carlos (IdISSC)Experimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de Investigación Sanitaria San Carlos (IdISSC)Experimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de Investigación Sanitaria San Carlos (IdISSC)START Madrid-FJD, Hospital Fundación Jiménez DíazSTART Madrid-CIOCC, Centro Integral Oncológico Clara CampalSTART Madrid-FJD, Hospital Fundación Jiménez DíazSan Carlos Clinical Hospital, OncologySan Carlos Clinical Hospital, OncologyDepartment of Bioinformatics, Semmelweis UniversityDepartment of Bioinformatics, Semmelweis UniversitySan Carlos Clinical Hospital, OncologySTART Madrid-CIOCC, Centro Integral Oncológico Clara CampalSTART Madrid-FJD, Hospital Fundación Jiménez DíazExperimental Therapeutics Unit, Hospital Clínico San Carlos (HCSC) Instituto de Investigación Sanitaria San Carlos (IdISSC)Abstract Genomic alterations in tumor cells can influence immune response, as has been demonstrated in several tumor types. For instance, mutations in certain genes like EGFR or B-RAF are associated with a particular immune phenotype. Non-small cell lung cancer (NSCLC) is one of the most immunogenic tumors, but certain genomic alterations can modulate and influence immune response. In the present work, we explore the transcriptomic landscape and immunologic profile of NSCLC with molecular alterations in SMARCA4. Using the TCGA repository we exploited their analysis with R and other available packages. cBioPortal was used to explore and analyze the mutational profile present in those tumors The prognostic value of identified genes in patients treated with immunotherapy was evaluated using the KMplotter online tool, and for correlations with immune populations TIMER 2.0 was interrogated. In lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) disruptive mutations in SMARCA4 were presented in 8%, and 4% of the cases, respectively. Gene deletions were observed in 1% of the population. The transcriptomic profile in LUAD and LUSC with deletions or disruptive mutations was explored. Interrogating TCGA using a 2.5 gene expression fold change (FC) we observed five genes commonly upregulated, and thirty-one genes commonly decreased when SMARCA4 was mutated or CNV loss was present. Enriched biological functions for downregulated genes included “Antigen processing and presentation, endogenous lipid antigen via MHC class Ib. Expression of CD1A, CD1C, CD1E, CX3CR1, and MYO1G showed a strong positive correlation with dendritic cells (DC) and dendritic cells resting (DCR). The increased expression of gene signatures formed by these transcripts resulted in a better prognosis in a set of patients with different tumors treated with anti-PD1 therapies, including 21 non-small cell lung cancers. We evaluated genomic alterations and transcriptomic patterns of SMARCA4 alterations in NSCLC tumors, identifying a relevant immunologic downregulated gene set linked with antigen presentation that predicts response to anti-PD1 therapies.https://doi.org/10.1038/s41598-025-02494-xLung adenocarcinomaLUADSMARCA4Immune responseImmunologic profile |
| spellingShingle | Cristina Nieto-Jiménez Esther Garcia-Lorenzo Cristina Diaz-Tejeiro Lucía Paniagua-Herranz Adrián Sanvicente Bernard Doger Irene Moreno Manuel Pedregal Jorge Bartolomé Arancha Manzano Gyöngyi Munkácsy Balázs Győrffy Pedro Pérez-Segura Emiliano Calvo Victor Moreno Alberto Ocana In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations Scientific Reports Lung adenocarcinoma LUAD SMARCA4 Immune response Immunologic profile |
| title | In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations |
| title_full | In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations |
| title_fullStr | In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations |
| title_full_unstemmed | In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations |
| title_short | In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations |
| title_sort | in silico evaluation of the immunogenic profile of lung cancers with smarca4 genetic alterations |
| topic | Lung adenocarcinoma LUAD SMARCA4 Immune response Immunologic profile |
| url | https://doi.org/10.1038/s41598-025-02494-x |
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