Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg
Introduction<p>Skin cutaneous melanoma (SKCM) is a highly aggressive form of cancer with poor prognosis, characterized by significant molecular and immune heterogeneity. The activation of KRAS signaling pathways is implicated in melanoma progression, yet its role in shaping the tumor microenvi...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2025
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| _version_ | 1852019241965846528 |
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| author | Beichen Cai (16842684) |
| author2 | Qian Lin (406644) Ruonan Ke (16842687) Jiaqi Yu (1874245) Lu Chen (75170) Xuejun Ni (8522640) Hekun Liu (5319638) Xiuying Shan (16842690) Biao Wang (288667) |
| author2_role | author author author author author author author author |
| author_facet | Beichen Cai (16842684) Qian Lin (406644) Ruonan Ke (16842687) Jiaqi Yu (1874245) Lu Chen (75170) Xuejun Ni (8522640) Hekun Liu (5319638) Xiuying Shan (16842690) Biao Wang (288667) |
| author_role | author |
| dc.creator.none.fl_str_mv | Beichen Cai (16842684) Qian Lin (406644) Ruonan Ke (16842687) Jiaqi Yu (1874245) Lu Chen (75170) Xuejun Ni (8522640) Hekun Liu (5319638) Xiuying Shan (16842690) Biao Wang (288667) |
| dc.date.none.fl_str_mv | 2025-06-18T05:45:56Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2025.1566432.s008 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Image_8_Identification_and_validation_of_a_KRAS-macrophage-associated_gene_signature_as_prognostic_biomarkers_and_potential_therapeutic_targets_in_melanoma_jpeg/29347742 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Genetic Immunology melanoma KRAS signaling macrophage infiltration prognostic biomarker immune microenvironment single-cell RNA sequencing |
| dc.title.none.fl_str_mv | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | Introduction<p>Skin cutaneous melanoma (SKCM) is a highly aggressive form of cancer with poor prognosis, characterized by significant molecular and immune heterogeneity. The activation of KRAS signaling pathways is implicated in melanoma progression, yet its role in shaping the tumor microenvironment, particularly in macrophage infiltration, remains poorly understood.</p>Methods<p>A comprehensive multi-platform approach was employed, analyzing gene expression data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was utilized to characterize the molecular pathways associated with KRAS signaling. Single-cell RNA sequencing (scRNA-seq) was leveraged to investigate the cellular heterogeneity within the SKCM tumor microenvironment, and macrophage populations were categorized using the Monocle2 algorithm. A KRAS-Macrophage Prognostic Associated Gene (KMPAG) signature was developed by integrating these findings, followed by validation using a least absolute shrinkage and selection operator (LASSO) regression model. The prognostic value of the KMPAG signature was assessed through its correlation with clinical outcomes, immune cell infiltration patterns, response to therapy, drug sensitivity, and miRNA-gene regulatory interactions. Cell-cell communication within the SKCM microenvironment was explored using the “CellChat” tool. Experimental validation of gene expression was performed via immunohistochemistry (IHC) and functional assays in gene-modified melanoma cell lines.</p>Results<p>Twenty-two genes involved in KRAS signaling were identified as critical for patient survival. Single-cell analysis revealed nine distinct cell populations within the SKCM microenvironment, leading to the construction of the KMPAG risk model, which incorporated three key genes—CLEC4A, CXCL10, and LAT2. This signature effectively reclassified macrophage subsets, offering improved diagnostic and prognostic capabilities. Furthermore, the KMPAG signature correlated with a range of clinical parameters, including immune infiltration levels, tumor stage, and therapy response. The model also provided insights into the immune landscape of SKCM, facilitating the prediction of responses to immunotherapy. Functional assays demonstrated that downregulation of CLEC4A significantly promoted melanoma cell proliferation, migration, and invasion.</p>Conclusion<p>This study highlights the importance of KRAS signaling and macrophage infiltration in melanoma prognosis. The KMPAG gene signature presents a novel prognostic tool, offering insights into personalized treatment strategies and predictive biomarkers for immunotherapy in SKCM. Further exploration of CLEC4A’s role in melanoma progression may provide new therapeutic avenues for targeted intervention.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_59b9dae8d9a4fa7d06bdbbc92df9b2d4 |
| identifier_str_mv | 10.3389/fimmu.2025.1566432.s008 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/29347742 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpegBeichen Cai (16842684)Qian Lin (406644)Ruonan Ke (16842687)Jiaqi Yu (1874245)Lu Chen (75170)Xuejun Ni (8522640)Hekun Liu (5319638)Xiuying Shan (16842690)Biao Wang (288667)Genetic ImmunologymelanomaKRAS signalingmacrophage infiltrationprognostic biomarkerimmune microenvironmentsingle-cell RNA sequencingIntroduction<p>Skin cutaneous melanoma (SKCM) is a highly aggressive form of cancer with poor prognosis, characterized by significant molecular and immune heterogeneity. The activation of KRAS signaling pathways is implicated in melanoma progression, yet its role in shaping the tumor microenvironment, particularly in macrophage infiltration, remains poorly understood.</p>Methods<p>A comprehensive multi-platform approach was employed, analyzing gene expression data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was utilized to characterize the molecular pathways associated with KRAS signaling. Single-cell RNA sequencing (scRNA-seq) was leveraged to investigate the cellular heterogeneity within the SKCM tumor microenvironment, and macrophage populations were categorized using the Monocle2 algorithm. A KRAS-Macrophage Prognostic Associated Gene (KMPAG) signature was developed by integrating these findings, followed by validation using a least absolute shrinkage and selection operator (LASSO) regression model. The prognostic value of the KMPAG signature was assessed through its correlation with clinical outcomes, immune cell infiltration patterns, response to therapy, drug sensitivity, and miRNA-gene regulatory interactions. Cell-cell communication within the SKCM microenvironment was explored using the “CellChat” tool. Experimental validation of gene expression was performed via immunohistochemistry (IHC) and functional assays in gene-modified melanoma cell lines.</p>Results<p>Twenty-two genes involved in KRAS signaling were identified as critical for patient survival. Single-cell analysis revealed nine distinct cell populations within the SKCM microenvironment, leading to the construction of the KMPAG risk model, which incorporated three key genes—CLEC4A, CXCL10, and LAT2. This signature effectively reclassified macrophage subsets, offering improved diagnostic and prognostic capabilities. Furthermore, the KMPAG signature correlated with a range of clinical parameters, including immune infiltration levels, tumor stage, and therapy response. The model also provided insights into the immune landscape of SKCM, facilitating the prediction of responses to immunotherapy. Functional assays demonstrated that downregulation of CLEC4A significantly promoted melanoma cell proliferation, migration, and invasion.</p>Conclusion<p>This study highlights the importance of KRAS signaling and macrophage infiltration in melanoma prognosis. The KMPAG gene signature presents a novel prognostic tool, offering insights into personalized treatment strategies and predictive biomarkers for immunotherapy in SKCM. Further exploration of CLEC4A’s role in melanoma progression may provide new therapeutic avenues for targeted intervention.</p>2025-06-18T05:45:56ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fimmu.2025.1566432.s008https://figshare.com/articles/figure/Image_8_Identification_and_validation_of_a_KRAS-macrophage-associated_gene_signature_as_prognostic_biomarkers_and_potential_therapeutic_targets_in_melanoma_jpeg/29347742CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/293477422025-06-18T05:45:56Z |
| spellingShingle | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg Beichen Cai (16842684) Genetic Immunology melanoma KRAS signaling macrophage infiltration prognostic biomarker immune microenvironment single-cell RNA sequencing |
| status_str | publishedVersion |
| title | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| title_full | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| title_fullStr | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| title_full_unstemmed | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| title_short | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| title_sort | Image 8_Identification and validation of a KRAS-macrophage-associated gene signature as prognostic biomarkers and potential therapeutic targets in melanoma.jpeg |
| topic | Genetic Immunology melanoma KRAS signaling macrophage infiltration prognostic biomarker immune microenvironment single-cell RNA sequencing |