{"title":"综合分析揭示 COL4A3 是紫外线相关皮肤皮肤黑色素瘤的新型诊断和治疗靶点","authors":"Zuochao Yao, Lu Lu, Qianhui Xu, Shan Hua, Hui Wang, Hua Jiang","doi":"10.2147/CCID.S461959","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>High levels of UV exposure are a significant factor that can trigger the onset and progression of SKCM. Moreover, this exposure is closely linked to the malignancy of the tumor and the prognosis of patients. Our objective is to identify a tumor biomarker database associated with UV exposure, which can be utilized for prognostic analysis and diagnosis and treatment of SKCM.</p><p><strong>Methods: </strong>This study used the weighted gene co-expression network analyses (WGCNA) and gene mutation frequency analyses to screen for UV-related target genes using the GSE59455 and the cancer genome atlas databases (TCGA). The prognostic model was created using Cox regression and least absolute shrinkage and selection operator analyses (LASSCO). Furthermore, in vitro experiments further validated that the overexpression or knockdown of COL4A3 could regulate the proliferation and migration abilities of SKMEL28 and A357 melanoma cells.</p><p><strong>Results: </strong>A prognostic model was created that included six genes with a high UV-related mutation in SKCM: COL4A3, CHRM2, DSC3, GIMAP5, LAMC2, and PSG7. The model had a strong patient survival correlation (<i>P</i>˂0.001, hazard ratio (HR) = 1.57) and significant predictor (<i>P</i>˂0.001, HR = 3.050). Furthermore, the model negatively correlated with immune cells, including CD8<sup>+</sup> T cells (Cor=-0.408, <i>P</i>˂0.001), and M1-type macrophages (Cor=-0.385, <i>P</i>˂0.001), and immune checkpoints, including programmed cell death ligand-1. Moreover, we identified COL4A3 as a molecule with significant predictive functionality. Overexpression of COL4A3 significantly inhibited the proliferation, migration, and invasion abilities of SKMEL28 and A357 melanoma cells, while knockdown of COL4A3 yielded the opposite results. And overexpression of COL4A3 enhanced the inhibitory effects of imatinib on the proliferation, migration, and invasion abilities of SKMEL28 and A357 cells.</p><p><strong>Conclusion: </strong>The efficacy of the prognostic model was validated by analyzing the prognosis, immune infiltration, and immune checkpoint profiles. COL4A3 stands out as a novel diagnostic and therapeutic target for SKCM, offering new strategies for small-molecule targeted drug therapies.</p>","PeriodicalId":10447,"journal":{"name":"Clinical, Cosmetic and Investigational Dermatology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192641/pdf/","citationCount":"0","resultStr":"{\"title\":\"Integrated Analysis Reveals COL4A3 as a Novel Diagnostic and Therapeutic Target in UV-Related Skin Cutaneous Melanoma.\",\"authors\":\"Zuochao Yao, Lu Lu, Qianhui Xu, Shan Hua, Hui Wang, Hua Jiang\",\"doi\":\"10.2147/CCID.S461959\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>High levels of UV exposure are a significant factor that can trigger the onset and progression of SKCM. Moreover, this exposure is closely linked to the malignancy of the tumor and the prognosis of patients. Our objective is to identify a tumor biomarker database associated with UV exposure, which can be utilized for prognostic analysis and diagnosis and treatment of SKCM.</p><p><strong>Methods: </strong>This study used the weighted gene co-expression network analyses (WGCNA) and gene mutation frequency analyses to screen for UV-related target genes using the GSE59455 and the cancer genome atlas databases (TCGA). The prognostic model was created using Cox regression and least absolute shrinkage and selection operator analyses (LASSCO). Furthermore, in vitro experiments further validated that the overexpression or knockdown of COL4A3 could regulate the proliferation and migration abilities of SKMEL28 and A357 melanoma cells.</p><p><strong>Results: </strong>A prognostic model was created that included six genes with a high UV-related mutation in SKCM: COL4A3, CHRM2, DSC3, GIMAP5, LAMC2, and PSG7. The model had a strong patient survival correlation (<i>P</i>˂0.001, hazard ratio (HR) = 1.57) and significant predictor (<i>P</i>˂0.001, HR = 3.050). Furthermore, the model negatively correlated with immune cells, including CD8<sup>+</sup> T cells (Cor=-0.408, <i>P</i>˂0.001), and M1-type macrophages (Cor=-0.385, <i>P</i>˂0.001), and immune checkpoints, including programmed cell death ligand-1. Moreover, we identified COL4A3 as a molecule with significant predictive functionality. Overexpression of COL4A3 significantly inhibited the proliferation, migration, and invasion abilities of SKMEL28 and A357 melanoma cells, while knockdown of COL4A3 yielded the opposite results. And overexpression of COL4A3 enhanced the inhibitory effects of imatinib on the proliferation, migration, and invasion abilities of SKMEL28 and A357 cells.</p><p><strong>Conclusion: </strong>The efficacy of the prognostic model was validated by analyzing the prognosis, immune infiltration, and immune checkpoint profiles. COL4A3 stands out as a novel diagnostic and therapeutic target for SKCM, offering new strategies for small-molecule targeted drug therapies.</p>\",\"PeriodicalId\":10447,\"journal\":{\"name\":\"Clinical, Cosmetic and Investigational Dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-06-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192641/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical, Cosmetic and Investigational Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/CCID.S461959\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical, Cosmetic and Investigational Dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/CCID.S461959","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Integrated Analysis Reveals COL4A3 as a Novel Diagnostic and Therapeutic Target in UV-Related Skin Cutaneous Melanoma.
Background: High levels of UV exposure are a significant factor that can trigger the onset and progression of SKCM. Moreover, this exposure is closely linked to the malignancy of the tumor and the prognosis of patients. Our objective is to identify a tumor biomarker database associated with UV exposure, which can be utilized for prognostic analysis and diagnosis and treatment of SKCM.
Methods: This study used the weighted gene co-expression network analyses (WGCNA) and gene mutation frequency analyses to screen for UV-related target genes using the GSE59455 and the cancer genome atlas databases (TCGA). The prognostic model was created using Cox regression and least absolute shrinkage and selection operator analyses (LASSCO). Furthermore, in vitro experiments further validated that the overexpression or knockdown of COL4A3 could regulate the proliferation and migration abilities of SKMEL28 and A357 melanoma cells.
Results: A prognostic model was created that included six genes with a high UV-related mutation in SKCM: COL4A3, CHRM2, DSC3, GIMAP5, LAMC2, and PSG7. The model had a strong patient survival correlation (P˂0.001, hazard ratio (HR) = 1.57) and significant predictor (P˂0.001, HR = 3.050). Furthermore, the model negatively correlated with immune cells, including CD8+ T cells (Cor=-0.408, P˂0.001), and M1-type macrophages (Cor=-0.385, P˂0.001), and immune checkpoints, including programmed cell death ligand-1. Moreover, we identified COL4A3 as a molecule with significant predictive functionality. Overexpression of COL4A3 significantly inhibited the proliferation, migration, and invasion abilities of SKMEL28 and A357 melanoma cells, while knockdown of COL4A3 yielded the opposite results. And overexpression of COL4A3 enhanced the inhibitory effects of imatinib on the proliferation, migration, and invasion abilities of SKMEL28 and A357 cells.
Conclusion: The efficacy of the prognostic model was validated by analyzing the prognosis, immune infiltration, and immune checkpoint profiles. COL4A3 stands out as a novel diagnostic and therapeutic target for SKCM, offering new strategies for small-molecule targeted drug therapies.
期刊介绍:
Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal.
Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest.
The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care.
All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.