DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma.
DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma.
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DNA 损伤修复相关基因特征可预测皮肤黑色素瘤的预后并指示免疫细胞浸润情况
DOI：
10.3389/fendo.2022.882431
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
DNA损伤修复在癌症的发生、发展及其对治疗的抵抗中起着重要作用。本研究旨在评估皮肤黑色素瘤（SKCM）中DNA损伤修复标记物的预后潜力。在这项研究中，我们分析了从TCGA，GTEx和GEO数据库下载的基因表达谱。我们依次使用单变量和LASSO考克斯回归分析来筛选与预后相关的DNA修复基因。然后，我们进行了多元回归分析，以构建DNA修复相关基因（DRRGs）的预后谱。风险系数用于计算风险评分并将患者分为两个队列。此外，我们在外部队列中验证了我们的预后模型，并评估了免疫应答与DRRGs预后特征之间的联系。将风险特征与免疫细胞浸润、化疗和免疫检查点抑制剂（ICI）治疗进行比较。使用LASSO-Cox逐步回归的分析建立了由12个具有强预测能力的DRRG组成的预后特征。高风险患者组的疾病特异性生存率（DSS）低于低风险患者组。在控制临床病理因素后，该特征可用作独立的预后预测因子，如通过对一个外部GSE 65904队列的验证所证明的。还发现风险评分与免疫微环境、沿着浸润免疫细胞和ICI关键分子之间存在强相关性。基因富集分析结果表明，高风险群体将表现出广泛的生物活性和途径。此外，顺铂在低风险组中表现出相当大的反应敏感性，而不是高风险事件，而多西他赛在高风险组中表现出相当大的反应敏感性。我们的研究结果对DRRG进行了彻底的调查，以开发一种与DSS相关的预后指标，该指标可能有助于预测SKCM进展并使免疫治疗的临床益处得到更多增强。
DNA damage repair plays an important role in the onset and progression of cancers and its resistance to treatment therapy. This study aims to assess the prognostic potential of DNA damage repair markers in skin cutaneous melanoma (SKCM). In this study, we have analyzed the gene expression profiles being downloaded from TCGA, GTEx, and GEO databases. We sequentially used univariate and LASSO Cox regression analyses to screen DNA repair genes associated with prognosis. Then, we have conducted a multivariate regression analysis to construct the prognostic profile of DNA repair-related genes (DRRGs). The risk coefficient is used to calculate the risk scores and divide the patients into two cohorts. Additionally, we validated our prognosis model on an external cohort as well as evaluated the link between immune response and the DRRGs prognostic profiles. The risk signature is compared to immune cell infiltration, chemotherapy, and immune checkpoint inhibitors (ICIs) treatment. An analysis using LASSO-Cox stepwise regression established a prognostic signature consisting of twelve DRRGs with strong predictive ability. Disease-specific survival (DSS) is found to be lower among high-risk patients group as compared to low-risk patients. The signature may be employed as an independent prognostic predictor after controlling for clinicopathological factors, as demonstrated by validation on one external GSE65904 cohort. A strong correlation is also found between the risk score and the immune microenvironment, along with the infiltrating immune cells, and ICIs key molecules. The gene enrichment analysis results indicate a wide range of biological activities and pathways to be exhibited by high-risk groups. Furthermore, Cisplatin exhibited a considerable response sensitivity in low-risk groups as opposed to the high-risk incidents, while docetaxel exhibited a considerable response sensitivity in high-risk groups. Our findings provide a thorough investigation of DRRGs to develop an DSS-related prognostic indicator which may be useful in forecasting SKCM progression and enabling more enhanced clinical benefits from immunotherapy.
影响因子：
5.2
作者：
Yang CC;Chang MT;Chang CK;Shyur LF
通讯作者：
Shyur LF