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一个用于快速确定头颈部鳞状细胞癌生存的七基因预后标志物。

A seven-gene prognostic signature for rapid determination of head and neck squamous cell carcinoma survival.

机构信息

Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.

NPFPC Contraceptive Adverse Reaction Surveillance Center, Jiangsu Institute of Planned Parenthood Research, Nanjing, Jiangsu, P.R. China.

出版信息

Oncol Rep. 2017 Dec;38(6):3403-3411. doi: 10.3892/or.2017.6057. Epub 2017 Oct 24.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and displays divergent clinical outcomes. Prognostic biomarkers might improve risk stratification and survival prediction. We aimed to investigate the prognostic genes associated with overall survival. A two-step gene selection method was used to develop a seven-gene-based prognostic model based on the training set collected from The Cancer Genome Atlas (TCGA). In addition, the prognostic model was validated in an independent testing set from Gene Expression Omnibus (GEO). The score based on the model successfully distinguished HNSCC survival into high-risk and low-risk groups in the training set (HR, 2.79; 95% CI, 1.98-3.92; P=4.05x10-9) and the testing set (HR, 2.05; 95% CI, 1.35-3.11; P=7.98x10-4). In addition, the score could significantly predict 5-year survival by ROC curves (AUCs for training set, 0.73; testing set, 0.66). Combining risk scores with clinical characteristics improved the AUCs beyond using clinical characteristics alone (training set, from 0.57 to 0.75; testing set, from 0.63 to 0.72). A subgroup sensitivity analysis with HPV status and tumor sites revealed that the risk score was significant in all subgroups except oral cavity tumors of the testing set. Furthermore, HPV-positive status improves survival in oropharyngeal HNSCC but not non-oropharyngeal HNSCC. In conclusion, the seven-gene prognostic signature is a reliable and practical prognostic tool for HNSCC. This approach can add prognostic value to clinical characteristics and provides a new possibility for individualized treatment.

摘要

头颈部鳞状细胞癌(HNSCC)是第六大常见癌症,具有不同的临床结局。预后标志物可能改善风险分层和生存预测。我们旨在研究与总生存期相关的预后基因。使用两步基因选择方法,基于从癌症基因组图谱(TCGA)收集的训练集开发了一个基于七个基因的预后模型。此外,在来自基因表达综合数据库(GEO)的独立测试集中验证了该预后模型。该模型基于评分成功地将 HNSCC 生存分为训练集(HR,2.79;95%CI,1.98-3.92;P=4.05x10-9)和测试集(HR,2.05;95%CI,1.35-3.11;P=7.98x10-4)的高风险和低风险组。此外,通过 ROC 曲线(训练集 AUC,0.73;测试集 AUC,0.66)评分可显著预测 5 年生存率。将风险评分与临床特征相结合,提高了 AUC 值,超过了仅使用临床特征(训练集,从 0.57 提高到 0.75;测试集,从 0.63 提高到 0.72)。HPV 状态和肿瘤部位的亚组敏感性分析表明,除了测试集中的口腔肿瘤外,风险评分在所有亚组中均具有统计学意义。此外,HPV 阳性状态可改善口咽 HNSCC 的生存,但不能改善非口咽 HNSCC 的生存。总之,该七个基因预后特征是 HNSCC 的可靠且实用的预后工具。这种方法可以为临床特征增加预后价值,并为个体化治疗提供新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4630/5783586/722d27b33eef/OR-38-06-3403-g01.jpg

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