Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma
Objective Cancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI in patients ≥80 years.Methods and analysis We analysed tumou...
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| Language: | English |
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BMJ Publishing Group
2025-01-01
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| Series: | BMJ Oncology |
| Online Access: | https://bmjoncology.bmj.com/content/4/1/e000551.full |
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| author | Abdul Rafeh Naqash April K Salama Emil Lou Andrew Elliott Wafik S El-Deiry Chul Kim Stephen V Liu Anwaar Saeed Hirva Mamdani Khalil Choucair Dipesh Uprety Phillip Walker Himisha Beltran Matthew James Oberley Azhar Saeed Lujia Chen |
| author_facet | Abdul Rafeh Naqash April K Salama Emil Lou Andrew Elliott Wafik S El-Deiry Chul Kim Stephen V Liu Anwaar Saeed Hirva Mamdani Khalil Choucair Dipesh Uprety Phillip Walker Himisha Beltran Matthew James Oberley Azhar Saeed Lujia Chen |
| author_sort | Abdul Rafeh Naqash |
| collection | DOAJ |
| description | Objective Cancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI in patients ≥80 years.Methods and analysis We analysed tumour samples (n=24 123) from patients ≥80 (versus<80) with non-small cell lung cancer (NSCLC), melanoma (MEL), and renal cell cancer (RCC). Using gene expression deconvolution, we investigated differences in tumour microenvironment (TIME) composition. Then, using next-generation sequencing and programmed death-ligand 1 (PD-L1) assessment, we evaluated gene expression differences between age groups and across tumour types, with a focus on ageing-related processes such as DNA damage response (DDR), immune checkpoint (IC) and metabolism-related genes. In a subset of patients ≥80 (n=1013), gene clustering and differential gene expression analyses were carried out to identify potential tumour-type specific expression patterns in responders to ICI.Results Significant differences in TIME composition were seen in patients with NSCLC and MEL. In patients ≥80, tumour mutational burden was lower in patients with NSCLC, higher in MEL and RCC had fewer PD-L1+tumours. DDR, IC and metabolism-related gene enrichments were distinct in patients ≥80. In patients ≥80 treated with ICIs (n=1013), there were no significant differences in survival between gene clusters, but differential gene expression analysis identified potential tumour-type specific expression patterns in responders.Conclusion Our findings reveal tumour type-specific expression profiles, TIMEs and response signatures to ICIs in patients ≥80, supporting further biomarker investigations in this population. |
| format | Article |
| id | doaj-art-3bc0d50004da42b2a9f5c7fc25ef91a7 |
| institution | Kabale University |
| issn | 2752-7948 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Oncology |
| spelling | doaj-art-3bc0d50004da42b2a9f5c7fc25ef91a72025-01-17T06:55:12ZengBMJ Publishing GroupBMJ Oncology2752-79482025-01-014110.1136/bmjonc-2024-000551Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinomaAbdul Rafeh Naqash0April K Salama1Emil Lou2Andrew Elliott3Wafik S El-Deiry4Chul Kim5Stephen V Liu6Anwaar Saeed7Hirva Mamdani8Khalil Choucair9Dipesh Uprety10Phillip Walker11Himisha Beltran12Matthew James Oberley13Azhar Saeed14Lujia Chen15Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USAAff2 grid.189509.c0000000100241216Melanoma Program, Division of Medical Oncology, Department of Internal MedicineDuke University Medical Center Box 2639 203 Research Drive, MSRB1, Room 397 27710 Durham NC USA10 Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA9Caris Life Sciences, Phoenix, AZ, USABrown University, Providence, Rhode Island, USA2 Division of Hematology and Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USAGeorgetown University, Washington, Washington, USA4 Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA2Barbara Ann Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA1Wayne State University, Detroit, MI, USA4Barbara Ann Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA3Caris Life Sciences, Phoenix, AZ, USA12Dana-Farber Cancer Institute, Boston, MA, USACaris Life Sciences, Phoenix, Arizona, USADepartment of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, USADepartment of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, USAObjective Cancer patients aged ≥80 years present unique characteristics affecting response to immune checkpoint inhibitors (ICIs), with unidentified molecular differences. This study aimed to explore potential biomarkers of response to ICI in patients ≥80 years.Methods and analysis We analysed tumour samples (n=24 123) from patients ≥80 (versus<80) with non-small cell lung cancer (NSCLC), melanoma (MEL), and renal cell cancer (RCC). Using gene expression deconvolution, we investigated differences in tumour microenvironment (TIME) composition. Then, using next-generation sequencing and programmed death-ligand 1 (PD-L1) assessment, we evaluated gene expression differences between age groups and across tumour types, with a focus on ageing-related processes such as DNA damage response (DDR), immune checkpoint (IC) and metabolism-related genes. In a subset of patients ≥80 (n=1013), gene clustering and differential gene expression analyses were carried out to identify potential tumour-type specific expression patterns in responders to ICI.Results Significant differences in TIME composition were seen in patients with NSCLC and MEL. In patients ≥80, tumour mutational burden was lower in patients with NSCLC, higher in MEL and RCC had fewer PD-L1+tumours. DDR, IC and metabolism-related gene enrichments were distinct in patients ≥80. In patients ≥80 treated with ICIs (n=1013), there were no significant differences in survival between gene clusters, but differential gene expression analysis identified potential tumour-type specific expression patterns in responders.Conclusion Our findings reveal tumour type-specific expression profiles, TIMEs and response signatures to ICIs in patients ≥80, supporting further biomarker investigations in this population.https://bmjoncology.bmj.com/content/4/1/e000551.full |
| spellingShingle | Abdul Rafeh Naqash April K Salama Emil Lou Andrew Elliott Wafik S El-Deiry Chul Kim Stephen V Liu Anwaar Saeed Hirva Mamdani Khalil Choucair Dipesh Uprety Phillip Walker Himisha Beltran Matthew James Oberley Azhar Saeed Lujia Chen Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma BMJ Oncology |
| title | Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma |
| title_full | Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma |
| title_fullStr | Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma |
| title_full_unstemmed | Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma |
| title_short | Molecular and immune landscape of tumours in geriatric patients with non-small cell lung cancer, melanoma and renal cell carcinoma |
| title_sort | molecular and immune landscape of tumours in geriatric patients with non small cell lung cancer melanoma and renal cell carcinoma |
| url | https://bmjoncology.bmj.com/content/4/1/e000551.full |
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