Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ul...Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.展开更多
本研究通过整合生物信息学分析与实验验证,系统探讨中胚层发育关键基因在黑色素瘤发生发展中的分子机制。基于基因集变异分析(gene set variation analysis,GSVA)算法对406例皮肤黑色素瘤(skin cutaneous melanoma,SKCM)患者的7752项生...本研究通过整合生物信息学分析与实验验证,系统探讨中胚层发育关键基因在黑色素瘤发生发展中的分子机制。基于基因集变异分析(gene set variation analysis,GSVA)算法对406例皮肤黑色素瘤(skin cutaneous melanoma,SKCM)患者的7752项生物功能进行富集分析,发现中胚层发育在黑色素瘤的发生发展中具有重要作用。通过LASSO-COX算法筛选出SMAD4、NODAL、BMPR1A和ZFP36L 1共4个核心调控基因,并构建预后相关风险评分体系。基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析显示,这些基因主要富集于mRNA代谢过程和TGF-β信号通路相关通路。通过定量聚合酶链式反应、蛋白质印迹及免疫组化证实:SMAD4和BMPR1A在肿瘤组织中的表达下调与不良预后显著相关(P<0.05);NODAL通过调控上皮-间质转化(EMT)过程促进肿瘤侵袭转移;ZFP36L1高表达组则表现出更好的化疗敏感性。进一步分析发现,核心基因表达水平与肿瘤免疫浸润特征及免疫检查点分子存在显著相关性。本研究通过多组学分析结合实验验证,揭示了中胚层发育相关基因在黑色素瘤进展中的关键作用,阐明了SMAD4/NODAL/BMPR1A/ZFP36L1通过免疫微环境调控和EMT过程影响肿瘤生物学行为的分子机制,为黑色素瘤的分子分型和靶向治疗提供了新的理论依据。展开更多
Skin cutaneous melanoma(SKCM)is a malignancy arising from the transformation of melanocytes in the basal layer of the epidermis,which accounts for over 75%of skin cancer-related deaths.1 Homeodomain-only protein homeo...Skin cutaneous melanoma(SKCM)is a malignancy arising from the transformation of melanocytes in the basal layer of the epidermis,which accounts for over 75%of skin cancer-related deaths.1 Homeodomain-only protein homeobox(HOPX)is the smallest member of the known homeodomain protein family in terms of relative molecular weight,and it was identified in 2002.2 Recently,it has been reported that HOPX can act as a tumor suppressor and is also able to participate in immune regulation,3,4 however,its role and mechanisms in SKCM and its modulation of immune cells remain unclear.Therefore,in this study,we aimed to investigate the role and mechanisms of HOPX on SKCM growth and its potential impact on macrophage polarization.展开更多
基金supported by the Natural Science Foundation of Hebei Province(Grant number:C2025405060).
文摘Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.
文摘本研究通过整合生物信息学分析与实验验证,系统探讨中胚层发育关键基因在黑色素瘤发生发展中的分子机制。基于基因集变异分析(gene set variation analysis,GSVA)算法对406例皮肤黑色素瘤(skin cutaneous melanoma,SKCM)患者的7752项生物功能进行富集分析,发现中胚层发育在黑色素瘤的发生发展中具有重要作用。通过LASSO-COX算法筛选出SMAD4、NODAL、BMPR1A和ZFP36L 1共4个核心调控基因,并构建预后相关风险评分体系。基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析显示,这些基因主要富集于mRNA代谢过程和TGF-β信号通路相关通路。通过定量聚合酶链式反应、蛋白质印迹及免疫组化证实:SMAD4和BMPR1A在肿瘤组织中的表达下调与不良预后显著相关(P<0.05);NODAL通过调控上皮-间质转化(EMT)过程促进肿瘤侵袭转移;ZFP36L1高表达组则表现出更好的化疗敏感性。进一步分析发现,核心基因表达水平与肿瘤免疫浸润特征及免疫检查点分子存在显著相关性。本研究通过多组学分析结合实验验证,揭示了中胚层发育相关基因在黑色素瘤进展中的关键作用,阐明了SMAD4/NODAL/BMPR1A/ZFP36L1通过免疫微环境调控和EMT过程影响肿瘤生物学行为的分子机制,为黑色素瘤的分子分型和靶向治疗提供了新的理论依据。
基金supported by the National Key Research and Development(R&D)Program of China(No.2022YFF0710503,2023YFF0724600)the Jilin Provincial Science and Technology Development Plan Project(China)(No.20230505037ZP)the Graduate Innovation Fund of Jilin University(China)(No.2024CX290).
文摘Skin cutaneous melanoma(SKCM)is a malignancy arising from the transformation of melanocytes in the basal layer of the epidermis,which accounts for over 75%of skin cancer-related deaths.1 Homeodomain-only protein homeobox(HOPX)is the smallest member of the known homeodomain protein family in terms of relative molecular weight,and it was identified in 2002.2 Recently,it has been reported that HOPX can act as a tumor suppressor and is also able to participate in immune regulation,3,4 however,its role and mechanisms in SKCM and its modulation of immune cells remain unclear.Therefore,in this study,we aimed to investigate the role and mechanisms of HOPX on SKCM growth and its potential impact on macrophage polarization.
