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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
NLR 相关预后特征的构建与鉴定揭示皮肤黑色素瘤中的异质性免疫反应
英文原题：Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma.
查看英文原题
Construction and Identification of an NLR-Associated Prognostic Signature Revealing the Heterogeneous Immune Response in Skin Cutaneous Melanoma.
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研究概要
开发了一种有前景的 NLRs 特征标签，对 SKCM 具有出色的预测效能。
中文摘要
背景
皮肤黑色素瘤（SKCM）是致死率最高的皮肤恶性肿瘤。持续研究已证实，NOD样受体（NLR）家族在驱动癌变中发挥重要作用。然而，NLR信号通路相关基因在SKCM中的功能仍不清楚。
目的
建立并验证与NLR相关的预后特征，并探索其预测SKCM患者异质性免疫反应的能力。
方法
采用最小绝对收缩与选择算子-Cox回归（LASSO-Cox）算法，基于NLR相关基因构建预测特征。通过单变量和多变量Cox分析验证该NLR特征的独立预测作用。使用CIBERSORT评估22种不同免疫细胞的相对浸润比例，并在临床样本中采用RT-qPCR和免疫组织化学验证关键NLR相关预后基因的表达。
结果
LASSO-Cox算法得到包含7个基因的预后特征。在TCGA及验证队列中，风险评分较高的SKCM患者总生存期明显较差；多变量Cox分析确认该特征具有独立预测作用。图形化列线图显示，NLR特征风险评分具有较高预测准确性。低风险患者呈现不同的免疫微环境，其炎症反应、干扰素反应和补体通路显著活化。多种抗肿瘤免疫细胞在低风险组显著富集，包括M1巨噬细胞、CD8 T细胞和活化NK细胞。该NLR预后特征可能成为预测免疫检查点阻断（ICB）治疗缓解率的候选标志物。表达验证（RT-qPCR和免疫组化）结果与此前分析一致。
结论
研究建立了一种具有良好SKCM预测效能的候选NLR特征。
展开英文摘要原文
BACKGROUND
Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear.
OBJECTIVE
To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients.
METHODS
Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature's independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples.
RESULTS
The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activated inflammatory response, interferon- / response, and complement pathways. Indeed, several anti-tumor immune cell types were significantly accumulated in the low-risk group, including M1 macrophage, CD8 T cell, and activated NK cell. It is worth noting that our NLRs prognostic signature could serve as one of the promising biomarkers for predicting response rates to immune checkpoint blockade (ICB) therapy. Furthermore, the results of expression validation (RT-qPCR and IHC) were consistent with the previous analysis.
CONCLUSION
A promising NLRs signature with excellent predictive efficacy for SKCM was developed.
论文信息
- 作者
- Geng Y、Sun YJ、Song H、Miao QJ、Wang YF、Qi JL、Xu XL、Sun JF
- 单位
- Institute of Dermatology, Peking Union Medical College and Chinese Academy of Medical Sciences, Nanjing, 210042, People's Republic of China.China
- 期刊
- Clinical, cosmetic and investigational dermatology2023
- 原文标识
- PubMed 37396711 · DOI 10.2147/CCID.S410723
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