Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status
Abstract Background Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis, often driven by asbestos exposure. Mutations in the NF2 gene, a key regulator of the Hippo signaling pathway, are frequently observed in PM. However, their impact on tumor biology, immune infiltration, cytokin...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-06-01
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| Series: | Journal of the Egyptian National Cancer Institute |
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| Online Access: | https://doi.org/10.1186/s43046-025-00284-0 |
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| author | Carlos Orozco-Castaño Alejandro Mejía-Garcia Hsuan Megan Tsao Diego A. Bonilla Carlos Carvajal-Fierro Ricardo Bruges-Maya Alba Combita Rafael Parra-Medina |
| author_facet | Carlos Orozco-Castaño Alejandro Mejía-Garcia Hsuan Megan Tsao Diego A. Bonilla Carlos Carvajal-Fierro Ricardo Bruges-Maya Alba Combita Rafael Parra-Medina |
| author_sort | Carlos Orozco-Castaño |
| collection | DOAJ |
| description | Abstract Background Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis, often driven by asbestos exposure. Mutations in the NF2 gene, a key regulator of the Hippo signaling pathway, are frequently observed in PM. However, their impact on tumor biology, immune infiltration, cytokine signaling, and therapeutic response remains poorly understood. Methods Using data from The Cancer Genome Atlas, we analyzed 82 PM cases to assess the prevalence and consequences of NF2 mutations. Logistic regression was used to evaluate associations with clinical variables, while transcriptomic differences were examined through differential expression and functional enrichment analyses. Immune and stromal infiltration were inferred via the xCell algorithm, cytokine signaling analyzed with Cytosig, and chemotherapeutic sensitivity predicted using the pRRophetic R package. Single-cell RNA sequencing data provided further insights into transcriptional patterns in NF2-mutated tumors. Results NF2 mutations were present in 22% of cases, with no significant correlations to histological subtype, stage, or age. NF2-mutated tumors exhibited increased infiltration of basophils, naïve B cells, and pericytes, along with altered cytokine profiles, including NRG1, TGFB3, and reduced FGF2. Differentially expressed genes, such as MYL7 and HOXA11, were linked to poorer survival. Chemotherapy modeling indicated higher sensitivity to camptothecin and vinblastine in NF2-mutated tumors. Conclusions NF2 mutations influence the tumor microenvironment, transcriptional landscape, and predicted therapeutic response in PM, underscoring their potential as prognostic biomarkers. These findings support tailored therapeutic strategies targeting NF2-related pathways, including Hippo signaling and cytokine modulation. |
| format | Article |
| id | doaj-art-4e6a1941e0a941908dc2df4ade6dc717 |
| institution | Kabale University |
| issn | 2589-0409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of the Egyptian National Cancer Institute |
| spelling | doaj-art-4e6a1941e0a941908dc2df4ade6dc7172025-08-20T04:01:35ZengSpringerOpenJournal of the Egyptian National Cancer Institute2589-04092025-06-0137111610.1186/s43046-025-00284-0Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational statusCarlos Orozco-Castaño0Alejandro Mejía-Garcia1Hsuan Megan Tsao2Diego A. Bonilla3Carlos Carvajal-Fierro4Ricardo Bruges-Maya5Alba Combita6Rafael Parra-Medina7Instituto Nacional de CancerologíaMcGill UniversityMcGill UniversityUniversity of the Basque CountryInstituto Nacional de CancerologíaInstituto Nacional de CancerologíaInstituto Nacional de CancerologíaInstituto Nacional de CancerologíaAbstract Background Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis, often driven by asbestos exposure. Mutations in the NF2 gene, a key regulator of the Hippo signaling pathway, are frequently observed in PM. However, their impact on tumor biology, immune infiltration, cytokine signaling, and therapeutic response remains poorly understood. Methods Using data from The Cancer Genome Atlas, we analyzed 82 PM cases to assess the prevalence and consequences of NF2 mutations. Logistic regression was used to evaluate associations with clinical variables, while transcriptomic differences were examined through differential expression and functional enrichment analyses. Immune and stromal infiltration were inferred via the xCell algorithm, cytokine signaling analyzed with Cytosig, and chemotherapeutic sensitivity predicted using the pRRophetic R package. Single-cell RNA sequencing data provided further insights into transcriptional patterns in NF2-mutated tumors. Results NF2 mutations were present in 22% of cases, with no significant correlations to histological subtype, stage, or age. NF2-mutated tumors exhibited increased infiltration of basophils, naïve B cells, and pericytes, along with altered cytokine profiles, including NRG1, TGFB3, and reduced FGF2. Differentially expressed genes, such as MYL7 and HOXA11, were linked to poorer survival. Chemotherapy modeling indicated higher sensitivity to camptothecin and vinblastine in NF2-mutated tumors. Conclusions NF2 mutations influence the tumor microenvironment, transcriptional landscape, and predicted therapeutic response in PM, underscoring their potential as prognostic biomarkers. These findings support tailored therapeutic strategies targeting NF2-related pathways, including Hippo signaling and cytokine modulation.https://doi.org/10.1186/s43046-025-00284-0Pleural mesotheliomaNF2 mutationsTranscriptome analysisChemotherapeutic responseImmune infiltrationPersonalized therapy |
| spellingShingle | Carlos Orozco-Castaño Alejandro Mejía-Garcia Hsuan Megan Tsao Diego A. Bonilla Carlos Carvajal-Fierro Ricardo Bruges-Maya Alba Combita Rafael Parra-Medina Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status Journal of the Egyptian National Cancer Institute Pleural mesothelioma NF2 mutations Transcriptome analysis Chemotherapeutic response Immune infiltration Personalized therapy |
| title | Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status |
| title_full | Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status |
| title_fullStr | Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status |
| title_full_unstemmed | Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status |
| title_short | Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status |
| title_sort | transcriptional landscape of pleural mesothelioma patients in relation to nf2 gene mutational status |
| topic | Pleural mesothelioma NF2 mutations Transcriptome analysis Chemotherapeutic response Immune infiltration Personalized therapy |
| url | https://doi.org/10.1186/s43046-025-00284-0 |
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