In silico evaluation of the immunogenic profile of lung cancers with SMARCA4 genetic alterations

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,...

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Veröffentlicht in:	Scientific reports Jg. 15; H. 1; S. 17832 - 11
Hauptverfasser:	Nieto-Jiménez, Cristina, Garcia-Lorenzo, Esther, Diaz-Tejeiro, Cristina, Paniagua-Herranz, Lucía, Sanvicente, Adrián, Doger, Bernard, Moreno, Irene, Pedregal, Manuel, Bartolomé, Jorge, Manzano, Arancha, Munkácsy, Gyöngyi, Győrffy, Balázs, Pérez-Segura, Pedro, Calvo, Emiliano, Moreno, Victor, Ocana, Alberto
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 22.05.2025 Nature Publishing Group Nature Portfolio
Schlagworte:	631/67/1612 631/67/68 Adenocarcinoma Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - immunology Antigen presentation Antigen processing Antigens Cancer Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - immunology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - immunology CD1c antigen Computer Simulation CX3CR1 protein Dendritic cells DNA Helicases - genetics Down-regulation Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes Genomics Humanities and Social Sciences Humans Immune response Immunogenicity Immunologic profile Immunotherapy LUAD Lung adenocarcinoma Lung cancer Lung Neoplasms - genetics Lung Neoplasms - immunology Lung Neoplasms - pathology Major histocompatibility complex multidisciplinary Mutation Non-small cell lung carcinoma Nuclear Proteins - genetics PD-1 protein Phenotypes Prognosis Raf protein Science Science (multidisciplinary) Small cell lung carcinoma SMARCA4 Squamous cell carcinoma Transcription Factors - genetics Transcriptome Transcriptomics Tumor cells Tumors Immune response Lung adenocarcinoma Immunologic profile LUAD SMARCA4
ISSN:	2045-2322, 2045-2322
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-025-02494-x