A 13-gene signature to predict the prognosis and immunotherapy responses of lung squamous cell carcinoma.
A 13-gene signature to predict the prognosis and immunotherapy responses of lung squamous cell carcinoma.
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DOI：
10.1038/s41598-022-17735-6
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发表时间：
2022-08-11
影响因子：
4.6
通讯作者：
Li, Hui
中科院分区：
文献类型：
--
作者：
Yang, Qin;Gong, Han;Liu, Jing;Ye, Mao;Zou, Wen;Li, Hui
肺鳞状细胞癌（LUSC）占所有肺癌的20-30%。免疫治疗显著改善了LUSC患者的预后;然而，只有一小部分患者对治疗有反应。因此，我们旨在开发一种与肿瘤微环境的免疫表型相关的新的多基因标记，用于LUSC预后预测。我们根据免疫细胞的浸润状态和PD-L1表达水平的组合，将来自癌症基因组图谱数据集的LUSC患者分层为热肿瘤和冷肿瘤。Kaplan-Meier分析显示，热肿瘤与较短的总生存期（OS）相关。热肿瘤和冷肿瘤之间差异表达基因（DEG）的富集分析表明，热肿瘤可能比冷肿瘤对免疫治疗具有更高的免疫应答率。随后，基于DEG的枢纽基因被鉴定，并构建蛋白质-蛋白质相互作用。最后，我们利用最小绝对收缩和选择算子特征选择和多元考克斯回归分析建立了一个基于hub基因的免疫相关的13基因签名。该基因特征将LUSC患者分为高风险组和低风险组，前者的OS比后者更差。多因素考克斯比例风险回归分析显示，13个预后基因构建的风险模型是影响预后的独立危险因素。受试者操作特征曲线分析显示1年、3年和5年OS的中等预测准确度。13个基因签名在来自Gene Expression Omnibus的4个外部队列（3个LUSC和1个黑素瘤队列）中也表现良好。总的来说，在这项研究中，我们建立了一个可靠的免疫相关的13个基因签名，可以分层和预测LUSC患者的预后，这可能有助于免疫治疗的临床应用。
Lung squamous cell carcinoma (LUSC) comprises 20–30% of all lung cancers. Immunotherapy has significantly improved the prognosis of LUSC patients; however, only a small subset of patients responds to the treatment. Therefore, we aimed to develop a novel multi-gene signature associated with the immune phenotype of the tumor microenvironment for LUSC prognosis prediction. We stratified the LUSC patients from The Cancer Genome Atlas dataset into hot and cold tumor according to a combination of infiltration status of immune cells and PD-L1 expression level. Kaplan–Meier analysis showed that hot tumors were associated with shorter overall survival (OS). Enrichment analyses of differentially expressed genes (DEGs) between the hot and cold tumors suggested that hot tumors potentially have a higher immune response ratio to immunotherapy than cold tumors. Subsequently, hub genes based on the DEGs were identified and protein–protein interactions were constructed. Finally, we established an immune-related 13-gene signature based on the hub genes using the least absolute shrinkage and selection operator feature selection and multivariate cox regression analysis. This gene signature divided LUSC patients into high-risk and low-risk groups and the former inclined worse OS than the latter. Multivariate cox proportional hazard regression analysis showed that the risk model constructed by the 13 prognostic genes was an independent risk factor for prognosis. Receiver operating characteristic curve analysis showed a moderate predictive accuracy for 1-, 3- and 5-year OS. The 13-gene signature also performed well in four external cohorts (three LUSC and one melanoma cohorts) from Gene Expression Omnibus. Overall, in this study, we established a reliable immune-related 13-gene signature that can stratify and predict the prognosis of LUSC patients, which might serve clinical use of immunotherapy.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
4
作者：
Santos ES;Hart L
通讯作者：
Hart L
人角蛋白：生物学和病理学。
影响因子：
2.3
作者：
Moll, Roland;Divo, Markus;Langbein, Lutz
通讯作者：
Langbein, Lutz
影响因子：
3.3
作者：
Feng, Xing-yu;Lu, Lin;Zhang, Xiao-shi
通讯作者：
Zhang, Xiao-shi
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T