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基于多组学研究放疗相关基因对黑色素瘤免疫浸润、免疫治疗反应及预后的影响

Research on the influence of radiotherapy-related genes on immune infiltration, immunotherapy response and prognosis in melanoma based on multi-omics.

作者信息

Shi Yujing, Zhao Wantong, Ding Yuanjian, Ge Xiaolin, Ju Mengyang

机构信息

Department of Oncology, Affiliated Jurong Hospital of Jiangsu University, Zhenjiang, ;China.

Department of Radiation Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, ;China.

出版信息

Front Immunol. 2024 Dec 2;15:1467098. doi: 10.3389/fimmu.2024.1467098. eCollection 2024.

DOI:10.3389/fimmu.2024.1467098
PMID:39687627
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11647020/
Abstract

BACKGROUND

Skin cutaneous melanoma (SKCM) is a significant oncological challenge due to its aggressive nature and poor treatment outcomes. This study explores the comprehensive effects of radiotherapy (RT) in SKCM, focusing on cell signaling pathways, immune infiltration, immune gene correlations, immunotherapy response, and prognosis.

METHODS

Using the Cancer Genome Atlas (TCGA) database, differentially expressed genes (DEGs) in SKCM patients undergoing RT were identified. A risk score model based on these DEGs was developed to assess the effects of RT-related genes on drug sensitivity, immune cell infiltration, immunotherapy response, and prognosis through multi-omics analysis. Human melanoma cells UACC62 and UACC257 were irradiated with 8 Gy gamma ray to establish an model, verifying the impact of radiotherapy on gene expression.

RESULTS

The risk score demonstrated significant prognostic value and emerged as an independent prognostic factor. miRNA-mRNA and transcription factor regulatory networks underscored its clinical significance. Four key genes were identified: DUSP1, CXCL13, SLAMF7, and EVI2B. Analysis of single-cell and immunotherapy datasets indicated that these genes enhance immune response and immunotherapy efficacy in melanoma patients. PCR results confirmed that gamma rays increased the expression of these genes in human melanoma cells UACC62 and UACC257.

CONCLUSION

Using a multi-omics approach, we analyzed and validated the impact of RT on the immune landscape of melanoma patients. Our findings highlight the critical role of RT-related genes in predicting SKCM prognosis and guiding personalized therapy strategies, particularly in the context of immunotherapy. These contribute to understanding the role of radiotherapy combined with immunotherapy in melanoma.

摘要

背景

皮肤黑色素瘤（SKCM）因其侵袭性本质和较差的治疗结果，是一项重大的肿瘤学挑战。本研究探讨了放射治疗（RT）在SKCM中的综合作用，重点关注细胞信号通路、免疫浸润、免疫基因相关性、免疫治疗反应和预后。

方法

利用癌症基因组图谱（TCGA）数据库，鉴定接受RT的SKCM患者中的差异表达基因（DEG）。基于这些DEG开发了一个风险评分模型，通过多组学分析评估RT相关基因对药物敏感性、免疫细胞浸润、免疫治疗反应和预后的影响。用人黑色素瘤细胞UACC62和UACC257接受8 Gy伽马射线照射以建立模型，验证放射治疗对基因表达的影响。

结果

风险评分显示出显著的预后价值，并成为一个独立的预后因素。miRNA-mRNA和转录因子调控网络强调了其临床意义。鉴定出四个关键基因：DUSP1、CXCL13、SLAMF7和EVI2B。单细胞和免疫治疗数据集分析表明，这些基因增强了黑色素瘤患者的免疫反应和免疫治疗疗效。PCR结果证实，伽马射线增加了这些基因在人黑色素瘤细胞UACC62和UACC257中的表达。

结论

我们采用多组学方法分析并验证了RT对黑色素瘤患者免疫格局的影响。我们的研究结果突出了RT相关基因在预测SKCM预后和指导个性化治疗策略中的关键作用，特别是在免疫治疗背景下。这些有助于理解放射治疗联合免疫治疗在黑色素瘤中的作用。

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