Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic mel...Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.展开更多
皮肤黑色素瘤免疫原性高,对传统治疗抵抗,免疫治疗是皮肤黑色素瘤治疗方案中的新兴手段,而疗效的差异性是亟待解决的问题,引发了对皮肤黑色素瘤免疫调控机制的探索。RNA N 6-甲基腺苷(m^(6)A)甲基化修饰在皮肤黑色素瘤的发生、发展、转...皮肤黑色素瘤免疫原性高,对传统治疗抵抗,免疫治疗是皮肤黑色素瘤治疗方案中的新兴手段,而疗效的差异性是亟待解决的问题,引发了对皮肤黑色素瘤免疫调控机制的探索。RNA N 6-甲基腺苷(m^(6)A)甲基化修饰在皮肤黑色素瘤的发生、发展、转移中发挥了重要作用。目前皮肤黑色素瘤主要通过肿瘤微环境、免疫检查点分子及其下游通路进行免疫调控,而m^(6)A调节因子参与其中。探索RNA m^(6)A甲基化修饰与皮肤黑色素瘤免疫调控机制的关系将有助于皮肤黑色素瘤免疫治疗的精准靶向,提高免疫治疗效果。展开更多
文摘Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.
基金supported by the Natural Science Foundation of Hunan Province(2021JJ30399)the Key Project of Health Commission of Hunan Province(202104122479),China。
文摘目的:黑色素瘤具有高度恶性和异质性。开发特定的黑色素瘤预后预测模型对提高患者的生存率和选择治疗策略至关重要。最近,铁死亡已被证明是一种由过度脂质过氧化诱导的铁依赖性程序性细胞死亡形式。然而,铁死亡相关基因(ferroptosis-related genes,FRGs)与黑色素瘤预后的相关性仍不清晰。本研究评估FRGs在黑色素瘤中的作用,开发一种新的预后模型,旨在为黑色素瘤的个性化治疗及疗效改善提供新思路。方法:首先通过系统地表征癌症基因组图谱(The Cancer Genome Atlas,TCGA)-皮肤黑色素瘤(skin cutaneous melanoma,SKCM)中73个FRGs的遗传改变和mRNA表达。同时通过反转录聚合酶链反应和蛋白质印迹法验证筛选的特定靶基因。随后使用TCGASKCM队列构建多基因特征模型。根据特征模型将黑色素瘤患者分为高风险和低风险组,对铁死亡相关的特征模型与免疫特征、免疫治疗的疗效或药物反应进行相关分析。结果:通过分析TCGA-SKCM数据集中的黑色素瘤样本,发现FRGs在基因变异和拷贝数变异方面表现出高频率,这些变化显著影响了基因的表达。此外,与正常皮肤组织相比,在黑色素瘤组织中发现了30个显著差异表达的基因。随后使用LASSO Cox回归方法构建的FRGs相关预后模型成功识别了13个与患者总体生存预后相关的FRGs,并通过外部数据集验证了该模型的有效性。最后,功能富集和免疫响应结果分析进一步表明高风险和低风险组之间存在免疫细胞浸润、突变负担和低氧状态的显著差异,且该模型能有效预测免疫治疗响应和药物敏感性。结论:本研究建立了一种强预后预测模型,可为黑色素瘤患者的靶向治疗和免疫治疗提供新的方向。
文摘皮肤黑色素瘤免疫原性高,对传统治疗抵抗,免疫治疗是皮肤黑色素瘤治疗方案中的新兴手段,而疗效的差异性是亟待解决的问题,引发了对皮肤黑色素瘤免疫调控机制的探索。RNA N 6-甲基腺苷(m^(6)A)甲基化修饰在皮肤黑色素瘤的发生、发展、转移中发挥了重要作用。目前皮肤黑色素瘤主要通过肿瘤微环境、免疫检查点分子及其下游通路进行免疫调控,而m^(6)A调节因子参与其中。探索RNA m^(6)A甲基化修饰与皮肤黑色素瘤免疫调控机制的关系将有助于皮肤黑色素瘤免疫治疗的精准靶向,提高免疫治疗效果。
