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Abstract：
BACKGROUND: One popular and well-established marker for the immune checkpoint blockade (ICB) response is tumor mutation burden (TMB). Persistent TMB (pTMB), a subset of TMB, provides a better indicator to predict patient ICB therapy outcomes, as shown by some studies. Immune checkpoint drugs have significantly changed how melanoma is treated in recent years.
METHODS: In this study, we integrated the TCGA-SKCM database and data of pTMB of TCGA from the paper that first mentioned pTMB and analyzed mutational and Immune characteristics associated with pTMB level in SKCM. Next, the predictive DEGs were identified the subgroups of pTMB by Cox regression and LASSO analyses to construct a pTMB-related signature. Finally, the expression and Biological functions of signature genes was detected, and further validated in vitro assay.
RESULTS: In the current research, we explored the mutational and immunological features related to the level of TMB in cutaneous melanoma (CM). The high-pTMB subgroup exhibited an increasing incidence of gene changes and higher levels of immune cell infiltration. Subsequently, we established a pTMB-related signature based on the predictive DEGs and found the biological features and immune-associated variables between two distinct risk groups. Lastly, the results of the clinical sample validation demonstrated that the expression of IL17REL was down-regulated in the collected samples of individuals with CM. The in vitro assay results indicated that IL17REL effectively suppressed the proliferation, clonality, and migration of CM cells.
CONCLUSIONS: In conclusion, we have developed a prediction model associated with TMB and subsequently validated the potential influence of IL17REL on Overall Survival (OS) in patients diagnosed with melanoma.
METHODS: In this study, we integrated the TCGA-SKCM database and data of pTMB of TCGA from the paper that first mentioned pTMB and analyzed mutational and Immune characteristics associated with pTMB level in SKCM. Next, the predictive DEGs were identified the subgroups of pTMB by Cox regression and LASSO analyses to construct a pTMB-related signature. Finally, the expression and Biological functions of signature genes was detected, and further validated in vitro assay.
RESULTS: In the current research, we explored the mutational and immunological features related to the level of TMB in cutaneous melanoma (CM). The high-pTMB subgroup exhibited an increasing incidence of gene changes and higher levels of immune cell infiltration. Subsequently, we established a pTMB-related signature based on the predictive DEGs and found the biological features and immune-associated variables between two distinct risk groups. Lastly, the results of the clinical sample validation demonstrated that the expression of IL17REL was down-regulated in the collected samples of individuals with CM. The in vitro assay results indicated that IL17REL effectively suppressed the proliferation, clonality, and migration of CM cells.
CONCLUSIONS: In conclusion, we have developed a prediction model associated with TMB and subsequently validated the potential influence of IL17REL on Overall Survival (OS) in patients diagnosed with melanoma.
摘要：
背景：免疫检查点阻断（ICB）反应的一种流行且公认的标志物是肿瘤突变负荷（TMB）。持久性TMB(pTMB)，TMB的子集，提供了更好的指标来预测患者ICB治疗结果，一些研究表明。近年来，免疫检查点药物显著改变了黑色素瘤的治疗方式。
方法：在本研究中，我们整合了TCGA-SKCM数据库和论文中首次提到pTMB的TCGA的pTMB数据，并分析了SKCM中与pTMB水平相关的突变和免疫特征。接下来,通过Cox回归和LASSO分析构建pTMB相关特征,将预测性DEGs识别为pTMB亚组.最后,标记基因的表达和生物学功能被检测,并在体外实验中进一步验证。
结果：在当前的研究中，我们探讨了与皮肤黑色素瘤（CM）中TMB水平相关的突变和免疫学特征。高pTMB亚组表现出基因变化的发生率增加和免疫细胞浸润的更高水平。随后，我们基于预测性DEGs建立了pTMB相关特征,并发现了两个不同风险组之间的生物学特征和免疫相关变量.最后,临床样本验证结果表明,在CM患者的采集样本中IL17REL的表达下调.体外实验结果表明IL17REL能有效抑制细胞增殖,克隆,和CM细胞的迁移。
结论：结论：我们建立了与TMB相关的预测模型,随后验证了IL17REL对诊断为黑色素瘤患者的总生存期(OS)的潜在影响.
方法：在本研究中，我们整合了TCGA-SKCM数据库和论文中首次提到pTMB的TCGA的pTMB数据，并分析了SKCM中与pTMB水平相关的突变和免疫特征。接下来,通过Cox回归和LASSO分析构建pTMB相关特征,将预测性DEGs识别为pTMB亚组.最后,标记基因的表达和生物学功能被检测,并在体外实验中进一步验证。
结果：在当前的研究中，我们探讨了与皮肤黑色素瘤（CM）中TMB水平相关的突变和免疫学特征。高pTMB亚组表现出基因变化的发生率增加和免疫细胞浸润的更高水平。随后，我们基于预测性DEGs建立了pTMB相关特征,并发现了两个不同风险组之间的生物学特征和免疫相关变量.最后,临床样本验证结果表明,在CM患者的采集样本中IL17REL的表达下调.体外实验结果表明IL17REL能有效抑制细胞增殖,克隆,和CM细胞的迁移。
结论：结论：我们建立了与TMB相关的预测模型,随后验证了IL17REL对诊断为黑色素瘤患者的总生存期(OS)的潜在影响.
